IL‐18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL‐18 production are found in the gene promoter region. We investigated the association of SNPs in the IL‐18 promoter at −607 and −137 with the level of IL‐18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL‐18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS‐stimulated IL‐18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL‐18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL‐18 gene influence the level of IL‐18 protein production by PBMC from healthy donors in Southwestern Siberia.

Tumor necrosis factor (TNF) is a key immunoregulatory cytokine with a dual role in the host response to Mycobacterium tuberculosis. While essential for granuloma formation, macrophage activation, and containment of latent infection, TNF can also contribute to tissue damage and immune pathology. This review systematically analyzes over 300 peer-reviewed studies published between 1980 and 2024, highlighting the molecular and cellular mechanisms of TNF action in tuberculosis (TB). Particular attention is given to TNF receptor signaling pathways, the balance between protective and pathological immune responses, and the modulation of TNF activity during anti-TNF therapy in patients with autoimmune diseases. We discuss how different TNF inhibitors vary in their capacity to interfere with host defense mechanisms, with monoclonal antibodies carrying a higher reactivation risk than receptor-based agents. To enhance conceptual clarity, we provide newly developed schematic representations that integrate current knowledge on TNF-driven immune dynamics, including its interaction with other cytokines, effects on granuloma stability, and role in intracellular bacterial control. Understanding the pleiotropic functions of TNF in tuberculosis pathogenesis is crucial for developing safe immunomodulatory strategies and optimizing the clinical management of patients at risk of latent TB reactivation.

Objectives: The aim of the study was to evaluate the potential contribution made by tumor necrosis factor (TNF) autoantibodies to the pathogenesis of bronchial asthma (BA). Methods: We used affinity chromatography methods and a magnetic separation procedure to purify human autoantibodies specific to TNF. The autoantibodies were used as a calibration material to determine the absolute content of autoantibodies to TNF using enzyme-linked immunosorbent assay (ELISA). TNF content and levels of soluble receptors to TNF were determined using the ELISA commercial test kits. Results: We demonstrated significant increases in the levels of TNF and soluble TNF receptors in the sera of patients with uncontrolled and controlled BA, as compared with healthy donors. Levels of autoantibodies of the IgG2 and IgG4 subclasses were significantly higher in sera from patients with uncontrolled BA than in healthy donors. Levels of IgG2 autoantibodies were significantly higher in sera from patients with uncontrolled BA than in patients with controlled BA. Conclusions: BA is associated with changes in the levels of not only TNF and soluble receptors for TNF, but also autoantibodies to TNF. Given the magnitude of the changes in the levels of different subclasses of autoantibodies to TNF, we propose that these autoantibodies might contribute to the pathogenesis of BA.

Background: Expression levels of cytokine and growth factor receptors have been found to be important in the regulation of their action. Tumor necrosis factor-α (