Department of Interferons

The department’s director is Professor A.N. Narovlyanskiy, Doctor of Biological Science.

The department was created in 1962 by USSR AMS academician V.D. Solovyov, who was in charge of it for almost 25 years. Over the years of its history, the department has turned into a well-known national center for studying physiology and the pathology of the interferon system. For more than 30 years, it has been actively working with the WHO and the International Cytokine & Interferon Society (ISICR).

There are well-known specialists that belong to the first generation of leading employees at the Department of Interferons: professors Ya.E. Khesin, V.P. Kuznetsov, I.G. Balandin, V.I. Marchenko, doctors of medical science N.R. Gutman and T.I. Krispin, Professor T.G. Orlova, and Doctor of Medical Science A.M. Sorokin.  These scientists, and their colleagues, have made significant contributions to how the problems involved in interferons have evolved in Russia, and to setting up a wide range of fundamental and clinical research studies.

Typically, the research that the department does is geared toward putting its scientific results into widespread medical practice. Here, back in the 1960s, the first drugs using human leukocyte interferons (IFN drugs) were created, which were successfully used in 1967 to help prevent influenza during epidemics.

Since the 1980s, the department has been involved in creating and using new, domestically-produced IFN inducers. The department has developed procedures that are widely used in clinics nowadays to determine the individual indicators for the state of the IFN system: the interferon status.

The first Russian monographs on the problems involved in interferons were the books written by F.I. Ershov and A.S. Novokhatskiy called The Interferon and Its Inducers (1980) and by V.D. Solovyov and T.A. Bektemirov Interferons in Medical Theory and Pratice (1981).

The main areas of focus for the department’s research are currently:

in the area of fundamental research:

Studying the patterns governing induction, production, and action on the part of alpha, beta, and gamma interferons, and other cytokines, at the levels of the molecule, cell, body, and population.

Deciphering the mechanisms that actualize the antiviral, immunomodulating, antitumorogenic, and other properties for interferons and their inducers

Determining the place of, and role played by, IFN systems in normal conditions and in various forms of infectious and non-infectious pathologies in both children and adults

in the area of applied research:

  • Improving the methods for determining IFN status, and making the informative value of its discrete indicators more explicit

  • Improving existing interferon drugs and their inducers, and creating new ones

  • Standardizing and streamlining the dosage schedule, and making scientifically validated determinations for the indications and contraindications for clinically using these drugs

  • On the medicinal use and comparative analysis of the efficacy for new interferon drugs, and their inducers, during various diseases

  • Developing scientifically validated methods to remedy congenital and acquired disorders of the IFN and cytokine systems.

In 2004, the cycle of studies done by F.I. Ershov, S.B. Cheknev, A.N. Narovlyanskiy, and M.V. Mezentseva called “The Interferon System in Conditions of Regulatory Imbalance: Assessing its State and Ability to be Remediated” was recognized with an N.F. Gamaleya RAMS Prize.

The results of the research done by the department are recapped in hundreds of scientific articles. Over the past 45 years, people at the department have defended 20 postdoctoral and more than 100 doctoral dissertations. Leading department employees are members of the Russian national chapter of the International Cytokine & Interferon Society (ISICR). The lion’s share of its work is done jointly with various Russian Academy of Sciences institutes, the Russian Ministry of Health, and with medical clinics and hospitals in Moscow and other Russian cities.

Laboratory of Ontogenesis and Interferon System Remediation

The director is Professor V.V. Malinovskaya, Doctor of Biological Science.

The laboratory was established in 1991.

The laboratory's research incorporates the long-term study of age-related characteristics of the IFN system: the relationship between the processes of interferonogenesis, lipid peroxygenation, and antioxidant defense. The result of this research was creating the integrated antiviral and immunomodulatory drug Viferon (in the form of rectal suppositories and ointment), which has the important advantage of an absence of the side effects that are typical for injectable forms of IFN.

Studying the various aspects of immunoreactivity, and doing assessments on the IFN status and cytokine profile assays, has made it possible to substantiate the use of this drug in integrated therapy in newborns, including premature babies, with intrauterine infections (herpes, chlamydia, cytomegaly, ureaplasma, and mycoplasmosis), infectious lesions of the central nervous system, and in pregnant women suffering from urogenital infections and bronchopulmonary pathologies. Using the drug can reduce the severity of the infection, and decrease the mortality rate among newborns.

Together with specialists from the Department of Children's Infectious Diseases at the Russian State Medical University (N.I. Pirogov Russian National Research Medical University), using Viferon in integrated treatment programs for chronic viral hepatitis in children has been scientifically and clinically validated. In terms of the efficacy of treating these diseases, the drug is on a par with injectable analogues. As part of integrated treatment, Viferon is successfully used in children afflicted with bronchial asthma, influenza, and acute respiratory infections.  Viferon ointment is effective in treating herpes infections, and to help prevent and treat influenza and acute respiratory infections.

Along with producing two dosage forms for Viferon, work is being performed further developing and putting new dosage forms for the drug into medical practice.

Six utility patents protect the laboratory’s scientific work and technological developments. In 2001, Professor V.V. Malinovskiy was issued a scientific discovery diploma for “The Pattern of Disruptions in the Spectrum of Interferons in the Blood of Children With Bronchial Asthma”, which was registered by the Russian Academy of Natural Sciences.

The research done by the laboratory is reflected in quite a few monographies:

  • O.Yu. Ustinova, V.V. Malinovskaya, V.F. Petrov, G.M. Volegova Interferon Therapy for Severe Forms of Tick-Borne Encephalitis Perm, 1997

  • A.M. Gerasimov, N.V. Delenyan, M.T. Shaov Formation of the Body's Antioxidant Defense System M., Deka, 1998

  • I.V. Nesterova, V.V. Malinovskaya, V.A. Tarakanov, S.V. Kovalyova Interferon Therapy and Immunotherapy in the Practice of Treating Children and Adults With Frequent and Long-Term Illnesses U.S. and Great Britain, Capricorn Publishing, Inc. 200 

Cytokine Laboratory

Laboratory director - Professor A.N. Narovlyanskiy, Doctor of Biological Science

The laboratory was established in 2002.

The main areas of focus for its research are:

  • Studying the mechanisms by which interferons act

  • Studying the role of cytokines that mediate how the IFN system is activated and its functions are regulated

  • Searching for anti-infectious drugs that regulate the activity of interferons and other cytokines.

Laboratory employees devote their attention to several areas of activity:

1. The cytokine-regulating activity of IFN inducers and other immunomodulators. The ability of IFN inducers, and other immunomodulators (polyprenyl phosphate, organic germanium compounds, compounds based on dipicolinic acid), to induce the expression of cytokine genes in model systems, both in vitro and in vivo and when a viral burden is present, is an area that is being studied. Similar studies are simultaneously being done that use peripheral blood mononuclear cells from both healthy volunteers and patients with infectious diseases (influenza and other acute respiratory infections, herpes, hepatitis, and sexually transmitted diseases).

2. Developing and studying IFN inducers to help prevent and treat viral infections. Efficacy on the part of IFN inducers when influenza, hepatitis C, HIV infection, or herpes are present is being researched. New methods are being employed for analyzing a prolonged IFN status, and to establish cytokine profiles.  Assessments are being done on the cellular sensitivity to the action of interferons and their inducers. Drawing on this, immunocorrective therapy is expected to be done that entails a customized selection of the most effective medicinal products.

3. Studying the isoprenoid system, which is considered one of the most phylogenetically ancient biological regulatory systems that is intrinsic to all living cells, from bacteria to humans. It is commonly known that insufficiency or defectiveness of the metabolic pathways in this system can lead to diseases that have various origins, and premature aging. The fact that polyisoprenoids participate in the formation of carbohydrate-containing biopolymers, and help maintain cell energy, is beyond doubt. The system plays a significant role in transmitting cell signals, modifying proteins, and stabilizing membranes. One of the objectives for the laboratory is to determine the role played by, and the place of, the system with isoprenoids, polyprenols, and dolichols, and their phosphates, in the life cycle of viruses and eukaryotic cells. Developing drugs that regulate the functioning of the isoprenoid system, and the studying the processes that it mediates, will lay the groundwork for a better understanding of the development mechanisms for quite a few serious human diseases, including viral and allergic diseases, immunodeficiencies, atherosclerosis, pancreatic necrosis, diabetes, multiple sclerosis, and Alzheimer's disease.

Research is being done jointly with the Russian Academy of Medical Sciences M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitis, the Russian Academy of Sciences N.D. Zelinskiy Institute of Organic Chemistry, and the Oak Ridge National Laboratory (USA). Using these studies as a foundation, a new antiviral drug with immunomodulatory activity was created (based on raw materials available in Russia and the USA), with preclinical and clinical trials done on the drug. The production technology and quality control methods for the new drug are being developed in parallel.

Laboratory of Antiviral Immunity

Laboratory director is Professor O.N. Scheglovitova, Doctor of Medical Science.

The laboratory was established in 2007. The main focus of its research is related to the studying the mechanisms governing antiviral immunity in cellular models of the infectious process, and in the infected bodies of humans and animals. In vitro modeling is implemented in cell cultures: on blood leukocytes and in primary cultures obtained from humans and animals. Along with that, unique primary cultures of endothelial cells (ECs) and smooth muscle cells (SMCs), isolated from the blood vessels in humans and animals, are used. These same models are utilized to study the antiviral and immunomodulatory effects of drugs.

One of the first workers that the laboratory ever had developed a model for the infectious process elicited by HIV-1 in ECs. This model was used to study the mechanisms governing the persistence of the virus, and the impact interferons and antiviral drugs have on the infectious process. The laboratory has adapted a model of the infectious process caused by HSV-1 in ECs. Research is being done on the mechanisms for the interaction between ECs, blood leukocytes, and SMCs in the pathogenesis of viral and somatic diseases.

The second direction of the laboratory's research is associated with studying the impact interferons and antiviral drugs have on the relationship between the infectious viral process and the functional state of the endothelium in blood vessels, assessed by the synthesis and expression of IFN and cytokines, cell adhesion molecules, and the factors that regulate vascular tone and have pro- and anti-coagulant effects that control fibrinolytic activity and angiogenesis.

The laboratory includes an interferon drug workgroup (director: D.L. Belyaev, PhD in Medical Science) Employees in this group (from what was formerly the interferon drug laboratory, which was created and operated on a constant basis for many years by Professor V.P. Kuznetsov), over decades of research, developed a technology to produce six dosage forms of IFN administered parenterally, locally, rectally, and via inhalation; the world's first integrated interferon and cytokine drug was created for the first step of the immune response: Leukinferon. Currently, a study is being done on the impact that immunocorrection has on hematopoiesis that has become depressed as a result of infectious lesions, stress, or aggressive treatment methods;  immunocorrection regimens are being developed for cases involving extensive surgical intervention and severe forms of infectious diseases that have a viral or microbial etiology, and have afflicted the respiratory, nervous and urogenital systems.

The website address for the Department of Interferons in the Internet is