Prospects for modulating the inflammatory process in recurrent ENT diseases

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.