Determination of interferons (“alpha”, “gamma”, serum, spontaneous) (venous blood) in Moscow


History of the discovery of interferon

Interferons (IFNs) belong to a special group of proteins that are produced by immune system cells in animals and humans. IFNs protect the body from pathogenic bacteria, parasites and even cancer cells. According to one version of scientists, thanks to interferons, humanity has not yet died from viral diseases.

The world learned about interferons not so long ago - only in the middle of the 20th century. And, despite the fact that many decades have passed since then, we can say that their discovery has become one of the most significant events in the medical world in the last and current century. In terms of scale, it is comparable only to the discovery of viruses themselves at the end of the 19th century.

Scientists were forced to think about the possible existence of some special protective barrier in the body by the phenomenon of interference, which consisted in the fact that after infection with certain viruses, cells become immune to viruses of another type. Scientists were most interested in the variant of interference in which the body, after the introduction of a non-pathogenic virus, became immune to infection by deadly pathogens. This method of protecting a person from diseases differs from the well-known vaccination, when by introducing a weakened or killed pathogenic agent they try to launch a specific system, i.e. acquired immunity.i

Interferons not only have antiviral activity (they were discovered by scientists for this reason), but also take a diverse role in the regulation of the immune response. Interferons as a system as a whole have a broader biological effect than limiting viral infection.ii

The mechanism of action of IFN is fundamentally different from antibodies. The fact is that IFNs are not specific to viral diseases and are able to fight different types of viruses. This means that medications containing interferons, which are intended for the prevention and treatment of acute respiratory viral infections, can fight not only a specific strain of influenza, for example, but all strains.

Detailed description of the study

Interferons (IFNs) are high molecular weight proteins that have mainly nonspecific antiviral activity. These proteins are produced by white blood cells after activation by viruses, bacteria or specific polysaccharides, proteins and drugs. Interferons have the ability to block viral replication, preventing damage to body cells. IFNs belong to the class of cytokines—small protein molecules that are used in signaling between cells to trigger an immune response against foreign pathogens.

According to the type of receptor with which interferon is able to transmit a signal, they are divided into the first (I), second (II) and third (III) types.

Type 1 interferons include IFN-alpha, including 13 subtypes. All type I interferons bind to a single cell surface receptor, type I IFN. They stimulate the JAK-STAT pathway, triggering the expression of IFN-stimulated genes that are associated with the body's antiviral defense. They have high activity against tumors and viruses, and also exhibit immunomodulatory properties.

Type II interferons, including only gamma IFN, are cytokines that play a huge role in innate and acquired immunity. They are produced by activation of T cells, natural killer (NK) cells and macrophages in response to cytokine stimuli such as IL-12. They have a pronounced immunomodulatory property; protection against tumors and viruses is less pronounced.

Type III interferons include IFN-delta and are divided into four subtypes. The mechanism of their action has been little studied to this day. The interferon response is formed much faster than the body’s specific defense reactions - this is an important indicator of immunity.

Interferon status is a group of indicators that characterizes the functioning of nonspecific immunity (IFN system). Interferon status determines the activity, adequacy and functionality of the interferon system. The activity of this system is reflected by four indicators:

  1. IFN-alpha secretion level;
  2. IFN-gamma secretion level;
  3. Serum IFN secretion level;
  4. Level of spontaneous IFN secretion.

IFN-alpha and IFN-gamma are assessed using stress tests. To determine these indicators, a specific agent is introduced into the human body to induce the production of interferons. Spontaneous IFN is determined without a specific load. Serum IFN reflects the total IFN content in the blood serum.

Determining a person's interferon status is necessary for several purposes. First, to determine the ability of the immune system to reproduce an adequate immune response in the event of an infectious lesion. Secondly, control the production of interferons at the time of illness. Thirdly, select effective immunomodulatory therapy.

Today, interferon preparations are actively used in medicine. Interferons indirectly induce a cascade of reactions, as a result of which proteins are synthesized that provide active protection against tumors and viruses.

Classification of interferons

The name “interferon” comes from the English “to interfere”, which is quite consistent with the action of these proteins - they interfere, i.e. prevent infection.

Today, more than 20 types of human interferons are known, which can be divided into three types:

  • The first type is antiviral interferons, which include interferon alpha (IFN-α), interferon beta (IFN-β), as well as some other interferons. The production of these IFNs begins when viruses, as well as some components of bacteria, enter the body. At the same time, other immune mechanisms are stimulated.
  • The second type is the so-called immune IFN, interferon gamma (IFN-γ). It acts as a second level of protection, i.e. is included in the fight against the disease after the “first wave” and activation of type 1 IFN. The antiviral and antitumor properties of this IFN are less pronounced than those of the previous group of IFNs.
  • The third type is represented by interferon lambda (IFN-λ), whose functions are still poorly understood. At the moment, its study is ongoing, but it has already been established that in its effect algorithm it resembles IFN alpha (IFN-α) and beta (IFN-β).

Review of the effectiveness of interferon alfa-2b drugs when administered intranasally

In the nearly 100 years since the Spanish Flu pandemic of 1918–1920, significant progress has been made in the fight against influenza and acute respiratory viral infections, but there is no talk of defeating them. The development and implementation of immunoprophylaxis methods into clinical practice entails a change in the antigenic structure of viruses, which, in turn, dictates the need to search for new antiviral agents. The constant need of society for effective drugs for the treatment and prevention of acute respiratory viral infections is reminiscent of the well-known evolutionary principle of the Red Queen: “you have to run as fast as you can just to stay in the same place” [5]. First of all, children of the younger age group (0–7 years) suffer from ARVI. Statistics show that respiratory tract diseases account for 90% of all infectious pathologies in children [3,6]. This is facilitated by the immaturity of the immune system, the anatomical features of the structure of the respiratory tract, the expansion of social contacts in connection with visiting organized children's groups, and the general tendency to reduce immunity [3,7,8]. At all stages of the formation of the immune system, the first barrier against the development of the infectious process is the local protection of the mucous membranes of the respiratory tract. Numerous viruses that enter the upper respiratory tract along with inhaled air are encountered with such factors of local immunity as viscous secretions, the movement of cilia of the mucociliary epithelium, the antiseptic properties of lysozyme and lactoferrin, the competing effect of natural microflora, the enzymatic activity of secretions, the specific action of IgA [7, 9,10]. Normally, local defense mechanisms have sufficient potential to prevent the infectious process in the early stages. But many weakening influences, including aggressive environmental conditions, the presence of chronic foci of infection, disruption of the microbiocenosis of saprophytic flora, largely limit the colonization resistance of mucous membranes [9,10]. In the event that an infectious agent is able to overcome local barriers due to high virulence, massive contamination of mucous membranes, and insufficient activity of protective mechanisms in situ, systemic immune reactions are activated. The features of local and general immunopathological reactions caused by the penetration of the pathogen into the body are important for the selection of key links in the therapeutic effect. ARVIs are diseases that require, first of all, pathogenetic treatment: this is due to the rapidity of their development, the danger of complications, and the difficulties of laboratory verification of the diagnosis [3]. The goal of therapy is to prevent the inflammatory process in the early stages. Knowing the basic patterns of immunity mechanisms, we can make the assumption that the effect on the interferon link is one of the most promising for the treatment and prevention of acute respiratory viral infections and represents a kind of trigger mechanism that can activate both local protective barriers of the mucosa and systemic humoral and cellular reactions. Interferons (IFNs) are endogenous protein molecules synthesized by immunocompetent cells in response to the penetration of a foreign agent. Several varieties of interferons are known, biologically similar, but with molecular differences and some features of immunotropic action. The most important in antiviral defense are type 1 IFNs (α, β). The mechanism of their action is the expression of genes that disrupt the penetration of the virus into the cell and the translation of viral proteins, as well as triggering apoptosis of infected cells [11]. In addition, IFNs participate in the cascade of cytokine reactions, inducing the production of TNF-α, IL-1, 6, 18 and other anti-inflammatory factors. It has been established that under the influence of IFN in the body, the activity of natural killer cells, cytotoxic T-lymphocytes, T-helpers, phagocytic activity, and the expression of HLA antigens of types 1 and 2 increases [7,11–15]. IFNs have been used in clinical practice for more than 30 years [11,12]. An important advantage of IFN drugs is their naturalness for the body, resulting in minimal toxicity and the possibility of administration to children [7]. The introduction of exogenous IFN allows you to mobilize antiviral protection faster than in the process of producing your own IFN, shorten the course and reduce the intensity of viral inflammation. In vitro, the ability of IFN to suppress the replication of most viruses was discovered when studying the phenomenon of viral interference [Lindenmann, Isaacs, 1957] and was subsequently confirmed in numerous studies. But the use of this effect for therapeutic purposes is limited by the systemic side effects of IFN when administered parenterally (intramuscular or subcutaneous). One of the main problems of interferon therapy is to “deliver” the effective dose of IFN directly to the site of inflammation, thus minimizing both the dose and the possibility of developing adverse events. Parenteral administration of IFN in high doses (for example, for viral hepatitis) entails various side effects caused by “cytokine shock”: fever, chills, arthralgia, headache. These symptoms are not critical for the body, because... are caused by fluctuations in their own humoral factors, but during the treatment process they cause inevitable discomfort for the patient. In the treatment of acute respiratory viral infections that do not require such high doses, the administration of suppository forms with a reduced content of recombinant human IFN-α made it possible to practically minimize the side effects of interferon therapy, while clinical, virological and immunological effectiveness was demonstrated. Rectal administration of recombinant human IFN in the first days of acute respiratory viral infection reduced the duration of fever, the severity of catarrhal symptoms, contributed to the elimination of the virus, and increased the number of T-lymphocytes (in particular, CD4+) [17,18]. But along with general immunomodulatory effects, it is advisable to use the ability of drugs to influence the local resistance of the mucous membranes of the respiratory tract in the fight against ARVI. The results of many studies show that correction of immune processes at the site of inflammation has a greater effect than the effect on immunocompetent cells of the bloodstream (with systemic use of drugs). Processes such as phagocytosis, antigen presentation, and lymphocyte cytotoxicity can be potentiated directly by local administration of immunocorrectors [22,25]. Therefore, a logical approach to the treatment of viral infections affecting the respiratory epithelium was the intranasal use of IFN drugs, which provide maximum effect at the site of development of the infectious process and thereby prevent ARVI at the earliest stages. Numerous studies have shown the high effectiveness of intranasal administration of IFN-α for ARVI [15,19–30]. In preclinical studies, the use of exogenous IFN significantly increased the level of secretory IgA, led to a significant decrease in replication, a decrease in the clinical and histological manifestations of influenza A, blocked its transmission, and prevented the development of complications of ARVI [19–25]. Type 1 IFN also enhanced the taxis of immunocompetent cells (in particular, CD8+ and CD4+ lymphocytes) to the site of infection [22]. Clinical studies have studied the effects of IFN-α when administered intranasally both for the treatment and prevention of acute respiratory viral infections. In a randomized clinical study of the effectiveness and safety of the use of IFN for the prevention of ARVI, patients in contact with the patient were prescribed intranasal IFN or placebo 2 times a day at the first signs of a cold. within 2 days. As a result, within the group receiving placebo, the number of people with clinical manifestations of ARVI was 55%, while in the group receiving IFN it was less than 13% [27]. In a study comparing 4-week use of IFN with placebo during a seasonal ARVI epidemic, a reduction in incidence of more than 75% was noted in the IFN group, while no effect was detected in the comparison group [28]. It is also known that in addition to the pronounced immediate antiviral effect, IFNs also provide systemic immunomodulation, thus increasing the body’s protective potential during the period of convalescence and reducing the number of repeated episodes of ARVI [18,26]. Currently, research is actively underway on local forms of IFN (in particular, lozenges for resorption containing 150,000 IU of recombinant human IFN-α) for the prevention and as part of complex therapy of seasonal ARVI [31]. As a means of preventing ARVI, IFNs are considered emergency preventive measures. They can be used immediately after contact with a patient, at the first symptoms of the disease and during the seasonal rise in the incidence of ARVI. Intranasal administration of IFN in the first hours after the onset of signs of a respiratory viral infection avoids its further development in more than 80% of cases [29]. It was found that the use of IFN together with the influenza vaccine is more effective for the prevention of ARVI than the isolated use of the vaccine [20], while in children, prophylaxis with intranasal IFN preparations compared to vaccination turned out to be more effective and better tolerated [30]. Recommended doses of IFN for the prevention of ARVI in adults are 50,000 IU three times a day. lasting up to 5 days. There are several types of dosage forms of IFN for local use: drops, ointment, gel, spray. The most appropriate for use in acute respiratory viral infections is a nasal spray, which allows for accurate dosing, uniform application, penetration into the deep parts of the nasal passages, and ease of use. The drug Genferon®Light in the form of a nasal spray is an effective and safe remedy for the prevention of acute respiratory viral infections in the early stages and the pathogenetic effect on the infectious process in the event of the development of the disease. In addition to recombinant human IFNα-2b, Genferon®Lite includes the amino acid taurine, which has cytoprotective, antioxidant, anti-inflammatory effects and enhances local protective and reparative processes at the site of inflammation. Genferon®Lite, containing a low dose of IFN (50,000 IU), virtually eliminates the possibility of side effects with the recommended dosage regimen, but due to its direct effect on the mucous membranes of the respiratory tract, it is no less effective than forms of IFN for systemic use. The effectiveness and safety of Genferon®Light nasal spray were proven in a double-blind, placebo-controlled clinical trial, which involved 100 patients with the first signs of ARVI. Patients in the main group (50 people) received Genferon®Lite at a dose of 50,000 IU 3 times a day. together with symptomatic therapy, and in the comparison group (50 people) - placebo. In the main group, such effects of IFN therapy were revealed as a decrease in the duration of headache and fever, a decrease in the severity of catarrhal symptoms, and accelerated elimination of viruses according to PCR results. In this regard, in the group receiving Genferon®Light, a significantly lower need for symptomatic therapy was noted [31]. Taking into account the above facts about the characteristics of local protective factors and the results of intranasal administration of IFN, it can be assumed that Genferon®Light nasal spray is one of the drugs of choice both as part of complex treatment and for the prevention of ARVI in adults and children. Literature 1. Smirnov V.S. Modern means of prevention and treatment of influenza and ARVI. – St. Petersburg: FARMIndex, 2008 – 48 p. 2. Ershov F.I. Rational pharmacotherapy of influenza and ARVI // Health of Ukraine. – 2003. – No. 4. 3. Scientific and practical program of the Union of Pediatricians of Russia // Acute respiratory diseases in children: prevention and treatment. A manual for doctors. – M., 2002. – 73 p. 4. Kiselev O.I., Ershov F.I., Sologub T.V., Romantsov M.G. H1N1 influenza as a typical emerging infection. A manual for doctors. – St. Petersburg–Kharkov–Uzhgorod, 2009. 5. Heylighen F., Van Valen L.The Red Queen Principle: new evolutionary law // Evolution. Theory. 1, 1–30. 6. Znamenskaya A.A., Fomina V.L., Uchaikin V.F. and others. Treatment and prevention of acute respiratory infections in frequently ill children // Pediatrics. – 2011. – No. 1. – P. 12–18. 7. Shcheplyagina L.A., Kruglova I.V. Age-related characteristics of immunity in children // Russian Medical Journal. – 2009. – No. 23. – P. 39–43. 8. Samsygina G.A. Frequently ill children: problems of pathogenesis, diagnosis and therapy // Pediatrics, supplement Consilium medicum. – 2004. – T. 6, No. 2 – P. 24–28. 9. Ryazantsev V., Khmelnitskaya N.M., Tyrnova E.V. The role of the mucous membrane in protecting the ENT organs from antigenic factors potentially pathogenic for the body // Bulletin of Otolaryngology. – 2001. – No. 6. – P.7–15. 10. Ovcharenko L.S., Vertegel A.A., Andrienko T.G. and others. The immune system of mucous membranes and associated lymphoid tissue: mechanisms of interaction in normal and pathological conditions, ways of correction // Clinical immunology, allergology, infectology. – 2008. – No. 4. – P.41–44. 11. Ershov F.I. The interferon system in normal conditions and in pathology - M.: Medicine, 1998 - 238 p. 12. Ershov F.I. The discovery of a biological phenomenon and its subsequent scientific knowledge. A brief essay on the 55-year history of the study of interferons and the contribution of domestic researchers to the development of this problem [Epub]. 13. Interferon status, interferon preparations in the treatment and prevention of infectious diseases and rehabilitation of patients / Ed. S.S Afanasyeva, G.G. Onishchenko, V.A. Aleshkina et al. - M., 2005. - 767 p. 14. Charles E. Samuel Antiviral actions of Interferons // Clin. Microbiol. Review. – 2001. Vol. 14(4). P. 778–809. 15. Mangan NE, Fung KY Type I interferons in regulation of mucosal immunity // Immunol. cell biol. 2012. Vol. 90(5). 16. Hsu AC–Y., Parsons K., Barr I. et al. Critical Role of Constitutive Type I Interferon Response in Bronchial Epithelial Cell to Influenza Infection // PLoS One. 2012. Vol. 7(3). 17. Kolobukhina L.V. Viferon in the treatment and prevention of acute respiratory viral infections // Russian Medical Journal. – 2003. – No.6. – pp. 47–50. 18. Feklisova L.V., Gorelov A.V., Drinevsky V.P. and others. The role of interferon drugs in the treatment of ARVI in infants and young children - results of a multicenter comparative randomized clinical trial // Pediatric Pharmacology. – 2011. – T. 8, No. 4 – P.33–37. 19. Neal Van Hoeven, Jessica A. Belser, Kristy J. Szretter et al. Tumpey Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding // J. Virol. 2009. Vol. 83(7). P. 851–861. 20. Robert B. Couch, Robert L. Atmar, Thomas R. Cate et al. Contrasting Effects of Type I Interferon as a Mucosal Adjuvant for Influenza Vaccine in Mice and Humans // Vaccine. 2009. Vol. 27(39). P. 344–348. 21. Kugel D., Kochs G., Obojes K. et al. Intranasal administration of alpha interferon reduces seasonal influenza A virus morbidity in ferrets // J. Virol. 2009. Vol. 83(8). P. 843–851. 22. Xi Y., Day SL, Jackson RJ, Ranasinghe C. Role of novel type I interferon epsilon in viral infection and mucosal immunity // Mucos. Immunol. 2012. Vol. 23 [Epub]. 23. Steel J., Staeheli P., Mubareka S. et al. Lowen Transmission of Pandemic H1N1 Influenza Virus and Impact of Prior Exposure to Seasonal Strains or Interferon Treatment // J. Virol. 2010. Vol. 84(1). P. 21–26. 24. Yohichi Kumaki, Jane Ennis, Ramtin Rahbar et al. Single–dose intranasal administration with mDEF201 (adenovirus vectored mouse interferon–alpha) confers protection from mortality in a lethal SARS–CoV BALB/c mouse model // Antiviral researches. 2011. Vol. 89(1). P. 75–82. 25. Schroder-Braunstein J., Pavlov V., Giese T. et al. Human mucosal CD4+ T cells but not blood CD4+ T cells respond strongly towards CD28 engagement // Clin. Experiment. Immunol. 2012. Vol. 168(1). P. 87–94. 26. Gurevich K.G. Prevention of seasonal acute respiratory viral infections // Medline. – 2001. – T. 2, No. 11 – P. 212–214. 27. Herzong C., Berger R., Fernex M. et al. Intranasal interferon (rIFN-alpha A, Ro 22-8181) for contact prophylaxis against common cold: a randomized, double-blind and placebo-controlled filed study // Antiviral Researches. 1986. No. 6. P.171–176. 28. Monto AS, Shope TC, Schwartz SA, Albrecht JK Intranasal interferon-alpha 2bretta for seasonal prophylaxis of respiratory infection // J. Infect. Diseases. 1986. No. 1. P.128–133. 29. Cantell K. Development of antiviral therapy with alpha interferons: promises, false promises and achievements // Annals of Med. 1995. No. 1. P. 23–28. 30. Kneyber MC, Moll HA, de Groot R. Treatment and prevention of respiratory virus infection // Eur. J. Pediatrics. 2000. No.6. P. 399–411. 31. Alpenidze D.N., Borzanova M.V., Maklakova E.V. and others. Modern approaches to the treatment of acute respiratory viral infections in adults - experience of clinical use of interferon alfa nasal spray // Handbook of a polyclinic physician. – 2010. – No.9. – P.19–23.

First production of interferon

For the first time, first-generation IFN preparations were obtained from leukocytes of donor blood. And immediately scientists began their clinical use and further study.

Science in the 20th century continuously developed, and over time, the basis for the biotechnological production of second-generation drugs containing recombinant IFNs was developed, i.e. obtained through genetic engineering.

Based on the method of production, IFN can be divided into 4 types:

  • leukocyte IFN, which is obtained from donor blood;
  • lymphoblastic IFN, obtained from the culture of lymphoblastic cells;
  • recombinant IFN, which is obtained using bacterial or fungal cultures;
  • pegylated types of IFN, which are obtained by combining recombinant IFN with a substance such as polyethylene glycol. In this way, pharmacists are trying to make the effect of the drug last longer.

The first production of IFN in the USSR was launched in 1988. At that time, these drugs were intended for the treatment of viral and oncological diseases. Great hopes were placed on interferons, so the study of these proteins was formed into a separate section of biology and medicine called interferonology. The scientific community actively began to develop a promising topic, as a result of which options for methods for determining the interferon status of the body were proposed.

At the moment, IFNs are considered as sufficiently studied immune mediators that have a wide range of biological activity and can be used not only in the prevention and treatment of viral diseases, but also non-viral diseases. Pharmacists have conducted many studies, with the help of which it was possible to prove that interferons occupy a leading position during therapy for such widespread and poorly controlled diseases as ARVI, hepatitis B, C and herpes.

References

  1. Lifshits, V.M., Sidelnikova, V.I. Medical laboratory tests. - M.: Triad X, 2007. - 312 p.
  2. Nesterova, I.V. Congenital and acquired interferonopathies: differentiated approaches to interferon-corrective therapy, Federal State Autonomous Educational Institution of Higher Education "Russian Peoples' Friendship University" of the Ministry of Education and Science of the Russian Federation, Moscow, 2021. - V. 16(2). — P. 50-53.
  3. Savenkova, M.S., Karashtina, O.V., Shabat, M.B. and others. Interferon status and choice of interferon inducers in frequently ill children. - Children's infections, 2021. - No. 2. - P. 45-51.

Are medications containing interferons suitable for children?

With acute respiratory viral infections and other viral diseases, children often experience a deficiency of interferons. For this reason, an additional source of IFN is needed to speed up recovery. Interferon, coming from outside, helps to mobilize the immune system of children and protects them from the development of complications.

Frequently ill children (FIC) require special attention, and this group includes not only preschoolers and schoolchildren who suffer from flu and colds more than 4-6 times a year, but also those who are ill for a long time - more than two weeks after each infection with ARVI. In such children, the production of natural IFN is reduced by no less than 15-20% compared to their peers. Medicines containing IFN not only fight viral diseases, but also enhance protective functions and help resist the disease.

For PBD, pediatricians recommend the use of long-term interferon therapy. Using this approach, it is possible to form a special IFN depot, due to which the cells in the body become resistant to the effects of infections.

Interferon ointment for children instructions for use

VIFERON ointment can be used to treat children over 1 year of age.

Herpes infection in young children.

For babies after one year of age, it is recommended to apply the drug to the affected areas 3-4 times a day for a course of 5 to 7 days. The drug can be used for all types of herpetic eruptions of various locations. And children under one year old can use VIFERON Gel.

In the treatment of influenza and ARVI

In children, as part of complex therapy, the ointment is prescribed:

  • From 1 year to 2 years: dosage 2500 IU (1 pea with a diameter of 0.5 cm) is applied in a thin layer to the mucous membrane of the nasal passages 3 times a day, course 5 days;
  • From 2 years to 12 years: a dosage of 2500 IU (1 pea with a diameter of 0.5 cm) is applied in a thin layer to the mucous membrane of the nasal passages 4 times a day, a course of 5 days;
  • From 12 to 18 years: a dosage of 5000 IU (1 pea with a diameter of 1 cm) is applied in a thin layer to the mucous membrane of the nasal passages 4 times a day, a course of 5 days.

To prevent colds, VIFERON Gel is used, as mentioned above. During the period of rising incidence, a strip of gel no more than 0.5 cm long is applied to the previously dried surface of the nasal mucosa and/or to the surface of the tonsils 2 times a day for 2-4 weeks.

Reference and information material

Author of the article

Gerasimenko Igor Olegovich

General Practitioner
Sources:

  • 1. https://humbio.ru
  • 2. State register of medicines
  • 3. https://www.sciencedirect.com
  • 4. https://www.who.int

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Are all “pherons” the same?

As already mentioned, some drug manufacturers produce drugs whose names contain the ending “...feron,” which can mislead the consumer and convince him that the drug contains interferons. In fact, these drugs may be homeopathic and do not contain IFN in any form. Homeopathy refers to alternative forms of medicine that involve the use of highly diluted drugs that are believed to cause disease-like symptoms in healthy people. Proponents of homeopathy contrast the concept of treatment according to the principle “like cures like” with the principles of rational pharmacotherapy.

Currently, homeopathic medicines may not undergo a full cycle of checks before being entered into the RLS (register of medicines), since a simplified registration form applies to them.

In 2021, scientists of the Russian Academy of Sciences (RAS) recognized homeopathy as a pseudoscience and came to the conclusion that its use in medicine “contradicts the main goals of domestic healthcare and should be met with organized government opposition.”

If you do not want to make a mistake, then before purchasing the medicine at the pharmacy, you should read the instructions and make sure that IFN is present in the composition. Trust reliable brands and pharmaceutical companies that have been known on the market for many years and have already won the trust of consumers.

Ointments with interferon: scope of application

These drugs are external, that is, drugs that are applied to the skin or mucous membrane. The effect of such a drug occurs on a limited surface, where it is applied. In other words, this dosage form is a local therapy drug. Like any medicine, interferon-based ointment is included in the register of medicines. The drugs included in the register have undergone the full range of studies and are approved by the Russian Ministry of Health for medical use. In what cases do doctors prescribe ointments containing this protein? As a rule, in cases where viruses of various origins are localized on human skin, creating a rash, neoplasms and other, including cosmetic, skin defects:

  • herpetic infection,
  • warts,
  • papillomavirus,
  • condylomas and so on.

To relieve the severity of inflammation and to prevent further spread of infection, as well as to fight viruses, it is recommended to apply the drug to the affected areas. How to choose the right medicine? When considering certain medications based on interferon, you need to pay attention to the dosage of the active substance in IU so that it corresponds to the dosage prescribed by the doctor, and, in addition, carefully read the instructions, especially the section that indicates age or other contraindications and restrictions for patients . It is worth paying attention to what is included in the drug, except for interferon. For example, one of the components of the drug VIFERON Ointment is peach oil. The composition of peach seed oil is surprisingly balanced. This is one of the rare oils, almost 40% of the vitamin content in which is vitamins PP and A, supplemented with ascorbic acid and vitamins E and B. Almost two-thirds of the fatty acid composition is oleic acid, another third is linoleic acid. These acids have wound healing and moisturizing properties. Peach oil has also been found to have antioxidant properties, which are known to help relieve symptoms of inflammation.

It must be remembered that there are medications that cannot be taken during pregnancy or breastfeeding, and there are also medications that are not recommended for children under a certain age. But there are others, for example, VIFERON Ointment, which are allowed for children from one year old, as well as for pregnant and lactating women.

Drugs that act on the immune system: what is the difference?

Immune drugs refer to special drugs that are of biological, plant or synthetic origin and can affect the immune system. The strength of their influence depends on the initial state of human immunity. In addition to modulators, immune drugs also include immunostimulants and immunosuppressants.

Immunostimulants strengthen the body's defenses against a particular infection. Those. the body is forced to resist, significantly strengthening cellular and humoral immunity. A distinctive feature of these drugs is the indiscriminate action of the immune system - a “shake-up” of the immune system. That is why this group of drugs must be used under the strict supervision of a doctor.

Immunosuppressants are designed to suppress the immune response. After all, sometimes immunity does not work for a person’s benefit, and then autoimmune diseases develop, in which the body’s own immune system destroys organs and tissues of the body. Immunosuppressants are also used during organ transplants to prevent rejection.

Immunomodulators are drugs that can have a targeted effect on a person’s immunity: they can increase low levels and decrease high levels, thus bringing the defenses back to normal. This is their main difference from immunostimulants and immunosuppressants. Medicines containing interferon are indicated for identified immunodeficiency of any etiology, for the treatment and prevention of various infectious and inflammatory diseases. Already today, many doctors advise the use of antiviral drugs with interferon to prevent and treat COVID-19 infection, as indicated by the national guidelines of the Ministry of Health of the Russian Federation.

The main criterion according to which a doctor prescribes immunomodulators is the clinical picture of the disease, which manifests itself as a chronic infectious-inflammatory process. Immunomodulators are also used to prevent a number of diseases.

Interferons (IFNs) are certain substances of protein origin, which are the most important component of innate nonspecific immunity, performing the function of protecting the body from various pathogenic microorganisms. For example, when confronted with a virus, interferons are capable of activating a whole cascade of reactions in the body aimed at fighting the infection.

Interferon-alpha (leukocyte) is considered the main one, produced by leukocytes synthesized in response to the invasion of pathogenic microorganisms. Main functions: antiviral (prevents the division of viral particles), activation of natural killer T-killers of the immune system, antitumor (by reducing cell proliferation and activating their apoptosis).

Determination of sensitivity to a specific antiviral drug, as a rule, is carried out in conjunction with an assessment of interferon status and involves determining the individual susceptibility of the body to the use of a particular drug.

Synonyms Russian

Selection of effective immunotherapy, monitoring the state of innate immunity.

Research method

Determination of biological activity to protect a cell culture monolayer from the CPD of the virus.

What biomaterial can be used for research?

Venous blood.

How to properly prepare for research?

  • Children under 1 year of age should not eat for 30-40 minutes before the test.
  • Do not eat for 2-3 hours before the test; you can drink clean still water.
  • Do not smoke for 30 minutes before the test.

General information about the study

Interferon (IFN) is the collective name for a number of protein compounds that are necessary to protect the body from infections and are an important component of innate nonspecific immunity. When viruses or other pathogenic substances enter the body, interferons activate intra- and extracellular mechanisms necessary for resistance or suppression of infection.

There is a classification of interferons, according to which they are divided into 3 types - alpha, beta and gamma interferons, each of which has its own characteristics both in structure and in the functions performed. Interferons alpha and beta are most similar and form class I type, interferons gamma – type II.

Interferon-alpha (leukocyte) is considered the main one, produced by leukocytes synthesized in response to the invasion of pathogenic microorganisms. Main functions: antiviral (prevents the division of viral particles), activation of natural killer T-killers of the immune system, antitumor (by reducing cell proliferation and activating their apoptosis).

Interferon-beta (fibroblastic) is formed in stimulated fibroblasts and performs functions similar to interferon-alpha.

Interferon-gamma (immune) is synthesized by T-lymphocytes and natural killer cells, also has antiviral and antitumor effects, but its main function is immunomodulatory (regulates the entire complex of immune responses in response to microorganism invasion).

After a viral particle enters the body, its cells begin to actively produce interferon. IFN does not have a direct antiviral effect, but is capable of activating cellular processes that block the division and spread of the virus. In addition, mechanisms of apoptosis of affected cells and protection of uninfected cells from possible effects are induced. Also, interferons (mainly gamma) promote the activation of the immune system to fight infection and control all cascades of reactions that occur during this process.

Currently, interferon preparations are widely used in medicine as antiviral agents, which provide the same biological effects as innate interferons synthesized in the body.

There is another group of drugs called interferon inducers, usually coming from the outside; they are capable of stimulating the synthesis and release of their own interferons and can induce the synthesis of a specific type of interferon or all of them at once, depending on the required indications for use.

There are also immunomodulators - substances that are able to control the processes and reactions of the immune system, usually aimed at strengthening existing immunity.

There are many drugs from all these groups, which differ somewhat in indications and purposes.

It is also necessary to note the presence of the interferon status of the body, the assessment of which allows one to draw conclusions about the state of the immune system, its potential and reserve capabilities in acute or chronic infectious processes. Assessment of IFN status is important, since interferon preparations, its inducers and immunomodulators are often used in the treatment of various infectious diseases. IFN status involves determining the biological functional activity of type I (alpha and beta) and type II (gamma) interferons and the level of biologically active interferon in the blood with determination of sensitivity to drugs. The study helps to evaluate the innate interferon system in the body and, if necessary, correctly prescribe appropriate therapy.

The study of the biological activity of IFN status is based on determining the antiviral effect of interferons in a biological test system (consists of a cell culture and a test virus with its damaging effect). As a result, the following indicators are determined:

  • serum (circulating) IFN, which is a combination of all types of IFN and the excess of which indicates an acute inflammatory process;
  • Type I IFN (alpha + beta) reflects the body's potential antiviral activity; in acute infectious diseases its decrease is most pronounced;
  • Type II IFN (gamma) reflects the state of the immune system; its decrease occurs predominantly in chronic immune-mediated disease.

Determination of sensitivity to certain antiviral drugs, as a rule, is carried out in conjunction with an assessment of IFN status and involves determining the individual susceptibility of the body to a particular drug. The results of the study allow us to optimally select therapy in each specific case and achieve the most effective response to it.

Indications for the study of IFN status with determination of sensitivity to drugs:

  • acute and chronic forms of viral infections;
  • recurrent (repeating) opportunistic infections (caused by opportunistic microorganisms);
  • examination of children who fall into the group of frequently ill people;
  • diagnosis of congenital and acquired defects of the interferon system;
  • allergic and autoimmune diseases;
  • selection of the most sensitive antiviral drugs for the treatment of a particular disease.

It is important to note that the results of the study must be assessed in conjunction with data from the clinical picture, anamnesis and other methods of laboratory and instrumental diagnostics. Interpretation is carried out only by a doctor in each clinical case individually.

Viferon is a preparation of interferon alpha-2b, has antiviral (suppresses viral replication), antiproliferative, immunomodulatory (enhances the phagocytic activity of macrophages and the specific action of lymphocytes) effect. Available in the form of rectal suppositories, ointment and gel. The ointment can be used in children from 1 year of age; other forms of release have no restrictions on use in children depending on age. The main indications for the use of Viferon: ointment - for herpetic infections and in the complex therapy of ARVI; gel – treatment and prevention of acute respiratory viral infections, laryngotracheobronchitis, herpetic infection; rectal suppositories - as part of the treatment of acute respiratory viral infections, infectious and inflammatory diseases of newborns, chronic viral hepatitis, herpetic infections. The main side effect when using Viferon is the development of allergic reactions. The drug treatment regimen is determined individually by the doctor, depending on the indications and purpose of therapy.

Determining sensitivity to Viferon allows you to assess the degree of susceptibility of each individual patient to this drug and predict how effective its use will be. This allows the doctor to select the most optimal management and treatment tactics, taking into account individual characteristics.

What is the research used for?

  • Selection of the most effective immunotherapy;
  • development of an individual regimen for the use of drugs for personalized treatment;
  • monitoring of treatment and prognosis of disease outcome;
  • in vitro diagnostics and monitoring of the state of innate immunity - assessment of the state of nonspecific resistance of the body.

When is the study scheduled?

  • Development of individual treatment regimens with interferon inducers;
  • assessment of the feasibility of interferon-stimulating therapy;
  • with long-term use of immunomodulatory drugs to monitor IFN status indicators;
  • assessment of innate immunity in diseases of various etiologies.

What do the results mean?

Interferon-gamma is a key cytokine, the level of production of which reflects the intensity of the cellular antiviral and antibacterial immune response.

The activity of the drug is assessed in comparison with the activity of type II IFN without this drug, which makes it possible to judge the sensitivity of human blood leukocytes to the drug under study.

Depending on the value of the indicator of IFN-γ production by leukocytes in the presence of drugs, according to the IFN status of a particular patient, the following degrees of sensitivity are distinguished:

Stimulation coefficient for the drug Degree of sensitivity to the drug Level of IFN-γ production
> 4 units/ml Strongly expressed Increases more than 4 times
2-4 units/ml Expressed Increases 2-4 times
2 units/ml Weakly expressed Increases 2 times
Lack of sensitivity Doesn't change

The results of a study of the functional biological activity of IFN by blood leukocytes must be considered in conjunction with anamnesis data, clinical data and the results of other diagnostic studies.

Interferon alpha 2 b as part of the antiviral drug VIFERON

The drug VIFERON is one of the antiviral drugs that have a wide spectrum of antiviral activity and help restore immunity. This drug contains recombinant interferon alpha-2b, which prevents the spread and reproduction of viruses in the body. It is identical to human interferon alpha-2b, which is synthesized naturally in human cells in response to foreign agents, but is produced using modern technology without the use of donor blood. Recombinant interferons belong to a group of antiviral drugs that are used for therapeutic and prophylactic purposes.

The drug in the form of suppositories is used in children and adults as part of complex therapy for the treatment of many diseases. When using the drug in the form of suppositories, the liver and stomach do not experience additional stress, which is very important for young children, people suffering from gastrointestinal diseases, including gastritis, as well as for older people.

It is worth noting that VIFERON does not belong to homeopathic remedies, but is a preparation of classical medicine. That is, to begin production, it had to go through all stages of clinical trials, as well as all kinds of quality checks (more than 250 indicators).

Interferon alpha 2b human recombinant as part of the drug VIFERON Gel

VIFERON Gel containing interferon alpha-2b is used for the prevention and treatment of acute respiratory viral infections, frequent and long-term acute respiratory viral infections, including those complicated by bacterial infection. In addition, the drug is used for the prevention and treatment of recurrent stenosing laryngotracheobronchitis - inflammation of the mucous membrane of the larynx and trachea, which leads to narrowing of the airway lumen and disruption of their functioning. When applied to the skin, mucous membrane and tonsils, the gel forms a thin protective layer, which prevents the penetration of viruses and also strengthens local immunity.

Also, the drug VIFERON Gel is used to treat acute and chronic herpetic infections of the skin and mucous membranes, including its urogenital form.

Interferon alpha 2 b as part of the drug VIFERON Ointment, instructions for use

VIFERON Ointment is an immunomodulatory and antiviral agent for external and local use. The ointment is produced in the form of a yellow or yellowish-white substance, viscous, homogeneous, with a specific odor of lanolin. The drug contains human recombinant interferon alpha-2b, tocopherol acetate, anhydrous lanolin, petroleum jelly, purified water and peach oil.

The drug VIFERON Ointment is used to treat ARVI, including influenza, as well as herpes of various localizations. For herpes (Herpes simplex types 1 and 2), the use of ointment leads to the complete disappearance of skin rashes.iii

Reference and information material

Shamsheva Daria Sergeevna

General practitioner, cardiologist, Ph.D.

Sources:

i

ii https://humbio.ru/

iii A.A. Khaldin, O.V. Chistik, D.V. Ignatiev “Herpes simplex: etiology, pathogenesis, diagnosis, treatment”, Practical Medicine No. 5, 2009

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Preparations with interferon: forms and contents

Modern pharmacology offers a huge selection of interferon-based drugs. They vary in dosage form, they can be: rectal suppositories, drops, gels, ointments, sprays, injection solutions and so on. They are no less diverse in composition: not all drugs are the same; they can often differ in the presence of auxiliary components, as well as in the dosage of the active substance. They have only one thing in common - the active substance itself, that is, interferon alpha-2b1, which is responsible in our body for fighting viruses and bacteria. This is a natural protein that is produced by the body in response to an infectious attack. It helps block the virus and protect healthy cells from infection, and also has a number of indirect antibacterial effects. Preparations containing this substance have been well studied and have been used for more than 50 years. Its main feature is a wide spectrum of antiviral activity, which allows doctors to use interferon-based drugs to treat various infectious and inflammatory diseases.

MEDICAL CENTER

  • Level of circulating interferon (serum interferon).
  • Spontaneous production of interferon in vitro.
  • Induced synthesis of alpha-interferon in vitro.
  • Induced synthesis of interferon gamma in vitro.

Additional tests:

  • Determination of sensitivity to interferon drugs (No. 1044 - Ingaron, No. 1045 - Intron, No. 1047 - Reaferon, No. 1048 - Realdiron, No. 1049 - Roferon).
  • Determination of sensitivity to interferon inducers (No. 1050 - Amiksin, No. 1051 - Kagocel, No. 1052 - Neovir, No. 1053 - Ridostin, No. 1054 - Cycloferon).
  • Determination of sensitivity to immunomodulators (No. 1055 - Galavit, No. 1056 - Gepon, No. 1057 - Immunal, No. 1058 - Imunofan, No. 1059 - Immunomax, No. 1060 - Likopid, No. 1061 - Polyoxidonium, No. 1062 - Taktivin, No. 1063 - Thymogen, No. 1066 - Imunorix, No. 1148 - Panavir, No. 1064 - Isoprinosine).

Interferons (IFNs) are the most important component of the body’s innate nonspecific defense against infections (the name interferons comes from their ability to interfere with viral infection of cells).
This is a family of proteins of local (autocrine and paracrine) regulation that are capable of activating intracellular processes and intercellular interactions that provide resistance to viral infections, enhance innate and acquired immune responses, modulate the processes of development and death of normal and tumor cells. The body's resistance to viral infections and a number of other diseases largely depends on the activity of a group of genes of the interferon system. Interferon preparations are widely used in medicine. The effects of interferons are indirect - activation of specific receptors by interferons causes a cascade of cellular processes leading to the induction of specific interferon-stimulated genes encoding the synthesis of many proteins, which provide the antiviral effects, antitumor and antiproliferative effects of interferons. Proteins induced by interferons include: enzymes, transcription factors, cell surface glycoproteins, cytokines, chemokines and other factors, the effect of which continues to be studied. The production of interferons by cells is transient, temporary - normally “silent” interferon genes are induced under the influence of products of viral and microbial origin and chemical inducers.

Interferons are divided into three types (α, β and γ), which are associated with specific functions and specific producing cells. Interferons α and β, despite significant structural differences, have common receptors and similar functions. Together they are also called type I interferons, or acid-stable interferons, in contrast to interferon-γ, which has its own receptors and partially different functions (it is also known as interferon II, or acid-labile interferon).

Interferon α (more than 20 of its subtypes have been identified) is the main interferon that is synthesized in a virus-induced leukocyte culture. The main producers of IFN-α are plasmacytoid dendritic cells; monocytes make a significant contribution to the IFN-α-producing ability of the blood. Its main functions are antiviral activity and activation of natural killer cells.

Interferon β is the main interferon produced by double-stranded RNA-induced fibroblast culture. Its main producers are fibroblasts, epithelial cells and macrophages; its main function is antiviral activity.

Interferon γ is the main interferon produced by immunologically stimulated (mitogens or antigens) lymphocyte cultures. The main producing cells of IFN-γ are T-lymphocytes. The main function of interferon gamma is immunoregulation (including activation of macrophages, enhancement of the Th1 response, induction of the expression of major histocompatibility complex type II antigens on antigen-presenting cells, etc.); like other interferons, it exhibits antiviral and antiproliferative activity. All animal cells are capable of producing interferons; certain cells (leukocytes and fibroblasts) can produce more than one type - both IFN-α and IFN-β.

Studying the parameters of interferon status allows us to identify insufficiency of the interferon system. Assessment of detected changes can serve as a guide in the diagnosis, treatment and prognosis of diseases of both viral and non-viral etiology. Healthy people are characterized by low levels of serum interferon and high values ​​of induced interferon synthesis. Stress and acute viral infections, allergic conditions are accompanied by an increase in the level of circulating interferon and a decrease in the level of induced production of alpha and gamma interferons by leukocytes. In bronchial asthma and urticaria, the level of circulating interferon correlates with the severity of the disease.

Chronic viral infections (herpes, hepatitis), multiple sclerosis are accompanied by suppression of all indicators of interferon status. Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis) are characterized by suppression of inducible production of interferon alpha. Acute lymphocytic leukemia and malignant formations are accompanied by suppression of induced interferon gamma production. The results of the study of interferon status should be considered in conjunction with other laboratory and clinical anamnestic data. A decrease in the production of alpha and gamma interferon, which can be both a cause and a consequence of acute and chronic viral diseases, indicates a congenital or acquired deficiency of the interferon system and can be considered as an indication for interferon-stimulating therapy. Normalization of interferon status indicators usually coincides with the recovery process. In people over 50 years of age, insufficiency of the interferon system is relatively more common. The study of interferon status parameters with determination of sensitivity to drugs is used to select effective therapy when using exogenous interferon drugs, interferon inducers and immunomodulators.

Interferon preparations

  • Ingaron is a recombinant human interferon-γ.
  • Intron - recombinant human interferon-α-2b.
  • Reaferon is a recombinant human interferon-α-2.
  • Realdiron is a recombinant human interferon-α-2b.
  • Roferon is a recombinant human interferon-α-2a.

Interferon inducers

  • Amiksin (international non-patent name - tilorone): dihydrochloride 2,7-bis-[2(diethylamino)-ethoxy]-fluorene-9-OH-dihydrochloride.
  • Kagocel: active substance - sodium salt of the copolymer (1-4)-6-0-carboxymethyl-bD-glucose, (1-4)-bD-glucose, (21-24)-2,3,14,15,21, 24,29,32-octahydroxy-23-(carboxy-methoxymethyl)-7,10-dimethyl-4,13-di(2-propyl)-19,22,26,30,31-pentaoxaheptacyclo [23.3.2.216.05.28 .08.27.09.1В.012.17] dotriaconta-1,3,5(28),6,8(27),9(18),10,12(17),13,1-decaene.
  • Neovir – 2-(9-oxo-9,10-dihydroacridin-10-yl) sodium acetate.
  • Ridostin is a mixture of sodium salts of double-stranded and single-stranded RNA.
  • Cycloferon – meglumine acridone acetate.

Immunomodulators

  • Galavit is a phthalhydrazide derivative.
  • Hepon is a synthetic peptide consisting of 14 amino acid residues.
  • Immunal is a preparation of Echinacea purpurea juice.
  • Immunofan is a hexapeptide (arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine).
  • Immunomax is an acidic peptidoglycan with a molecular weight of 1,000 - 40,000 kDa.
  • Lykopid - active substance - glucosaminylmuramyl dipeptide - 4-O-(2-acetylamino-2-deoxy-beta-D-glucopyranosyl)-N-acetylmuramyl]-L-alanyl-D-alpha-glutalamide.
  • Polyoxidonium - international non-proprietary name / composition: Azoximer (Azoximer) - N-oxidized derivative of polyethylene piperazine.
  • Taktivin is a complex of polypeptides from the thymus gland of cattle.
  • Thymogen is a polypeptide from the thymus gland of cattle.
  • Panavir is a purified extract of shoots of the Solanum tuberosum plant, the main active ingredient is a hexose glycoside consisting of glucose, rhamnose, arabinose, mannose, xylose, galactose, uronic acids.
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