Prospects for modulating the inflammatory process in recurrent ENT diseases

Savlevich E.L., Zurochka A.V., Yastremsky A.P., Kartashova M.K., Kozulina I.E., Tumanova E.A., Popadyuk V.I., Kabanova T.G., Kozlov I.G.

1) M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia; 2) Clinical Hospital of the Administrative Directorate of the President of the Russian Federation, Moscow, Russia; 3) Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia; 4) Federal Research Institute of Viral Infections “VIROM”, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Yekaterinburg, Russia; 5) Tyumen Medical University, Tyumen, Russia; 6) I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 7) Peoples’ Friendship University of Russia named after Patrice Lumumba, Moscow, Russia; 8) Sverdlovsk Regional Clinical Hospital No. 1, Yekaterinburg, Russia

Acute and chronic inflammatory ENT-diseases are the most common pathological conditions worldwide. The primary goal of treating acute upper respiratory tract inflammation (URTI) is to reduce the severity of the infection and transform it into a form with mild clinical symptoms, which could prevent the development of complications and long-term effects after a respiratory infection. Acute inflammatory ENT-diseases of the organs should progress through all stages of a typical pathological process, ending in recovery. However, in some situations, the inflammatory process fails to progress to either a complete resolution phase or a chronic proliferative phase. This means the infection cannot resolve, clinically manifesting as a sluggish, torpid course. This condition may be caused by incomplete phagocytosis, an imbalance between the M1 and M2 macrophage fractions, a hypoergic inflammatory process, or pathogen persistence. Targeted stimulation of macrophages toward the M1 phenotype abruptly shifts the system from equilibrium toward acute inflammation. Proinflammatory cytokines IL-1β, IL-6, and TNF-α are released, triggering NETosis, which then stimulates the M1 → M2 macrophage transition, which in turn begins to produce anti-inflammatory cytokines IL-10 and TGF-β. M2 macrophages destroy all cellular debris, stimulating proliferation and the healing process. Thus, it is the stimulation of M1 macrophages and their subsequent transition to the M2 phenotype that effectively helps combat protracted, sluggish inflammation, creating a «proinflammatory flare,» which is the necessary impetus for the full and complete cycle of the inflammatory response. Glucosaminylmuramyl dipeptide (Likopid) exerts its biological activity by binding to the intracellular receptor protein NOD2, triggering phosphorylation of interferon regulatory factor (IRF)-3, thereby increasing IFN-α production and enhancing the production of proinflammatory cytokines IL-1β, IL-6, IL-12, TNF-α, the chemokine CXCL-8, IFNγ, and colony-stimulating factors. Subsequently, the cytosolic NOD2 receptor is translocated to the cytoplasmic membrane and translocated with DUOX2, which encodes dual oxidase type 2, a protein in the hydrogen peroxide generation system, enhancing the bactericidal effect and promoting inflammation regression. The clinical activity of Likopid has been confirmed in recurrent acute and chronic rhinosinusitis, tonsillopharyngitis, including those associated with persistent Epstein-Barr virus (EBV), allergic rhinitis, and in patients with post-COVID syndrome.

For citations: Savlevich E.L., Zurochka A.V., Yastremsky A.P., Kartashova M.K., Kozulina I.E., Tumanova E.A., Popadyuk V.I., Kabanova T.G., Kozlov I.G. Prospects for modulating the inflammatory process in recurrent ENT diseases. Pharmateca. 2025;32(9):31-39. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2025.9.31-39

Authors’ contribution: E.L. Savlevich – article concept and design, writing the text. A.V. Zurochka – article concept and design, writing the text. M.K. Kartashova – writing the text, creating figures. I.E. Kozulina – collecting and processing the materials. T.G. Kabanova – editing the text. A.P. Yastremsky – writing the text. E.A. Tumanova – collecting and processing the materials, writing the text. V.I. Popadyuk – editing the text. I.G. Kozlov – article design, editing the text.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.

Keywords

About the Authors

Elena L. Savlevich, Associate Professor, Dr. Sci. (Med.), Otolaryngologist, M.F. Vladimirsky Moscow Regional Research Clinical Institute; Clinical Hospital of the Administrative Directorate of the President of the Russian Federation, Moscow; savllena@gmail.com, ORCID: https://orcid.org/0000-0003-4031-308X, Scopus ID: 56769915400, eLibrary SPIN: 7000-3714 (corresponding author)
Aleksandr V. Zurochka, Dr. Sci. (Med.), Professor, Leading Researcher, Laboratory of Immunopathophysiology, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences (Yekaterinburg); Professor, Department of Food and Biotechnology, South Ural State University (National Research University), Chelyabinsk, Russia; av_zurochka@mail.ru, ORCID: https://orcid.org/0000-0003-4371-4161
Andrey P. Yastremsky, Dr. Sci. (Med.), Professor, Head of the Department of Otolaryngology, Tyumen Medical University, Tyumen, Russia; yastrem-andrej97@yandex.ru, ORCID: https://orcid.org/0000-0002-7760-4860, Scopus ID: 56728747900, eLibrary SPIN: 8186-5360
Maria K. Kartashova, Teaching Assistant, Department of Pathological Physiology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; kartashova_m_k@staff.sechenov.ru, ORCID: https://orcid.org/0000-0003-2135-1662
Irina Evgenyevna Kozulina, Cand. Sci. (Med.), Assistant Professor, Department of Allergology and Immunology, Faculty of Continuous Postgraduate Education, Peoples’ Friendship University of Russia named after Patrice Lumumba, Moscow, Russia; IKozulina@gmail.com, ORCID: https://orcid.org/0000-0002-8067-5387
Ekaterina A. Tumanova, Otorhinolaryngologist, Otolaryngology Department, Sverdlovsk Regional Clinical Hospital No. 1, Yekaterinburg, Russia; innatumanowa@yandex.ru, ORCID: https://orcid.org/0009-0004-7558-3906
Valentin I. Popadyuk, Dr.Sci. (Med.), Professor, Head of the Otolaryngology Department, Peoples’ Friendship University of Russia named after Patrice Lumumba, Moscow, Russia; lorval04@mail.ru, ORCID ID: https://orcid.org/0000-0003-3309-4683
Tatyana G. Kabanova, Cand. Sci. (Med.), Head of the Multidisciplinary Day Hospital, M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia; kabanova75@yandex.ru, ORCID: https://orcid.org/0009-0000-0990-2535, eLibrary SPIN: 9358-1745
Ivan G. Kozlov, Dr. Sci. (Med.), Professor, Department of Organization and Management in Medicine Circulation, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; immunopharmacology@yandex.ru, ORCID: https://orcid.org/0000-0002-9694-5687

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