Current issue

Adipocytes, immune cells, and cells of the stromal vascu­lar fraction are sources of many biologically active substances. The effects of most adipocytokines are well studied; however, the role of individual molecules secreted by adipose tissue in the patho­genesis of inflammation associated with metabolic syndrome (MS) and related diseases has not been fully elucidated and remains a matter of debate.

Aim — To evaluate the expression of adipocytokine genes in biop­sies (fragments) of visceral adipose tissue of the gastrocolic omen­tum in patients with MS.

Materials and methods. The study included 19 patients: the main group — 14 patients with MS, the comparison group — 5 patients without MS. The level of expression of cytokine genes (IL1B, IL6, IL8, TNF-α) and peptide hormones (LEP (leptin), NAMPT (visfatin), RETN (resistin), ADIPOQ (adiponectin)) was studied in biopsies of adipose tissue of the greater omentum obtained during planned cholecystectomy for medical reasons by the level of matrix RNA using quantitative real-time PCR with preliminary development of complementary DNA in the reverse transcription reaction.

Results. There were no significant differences in the level of mRNA of IL-1B, -6, -8, TNF-α, as well as the hormones LEP, NAMPT, RETN in adipose tissue in patients with MS and in the comparison group (р > 0.05). Statistically significant differences were established only in the level of ADIPOQ gene expression: the level of ADIPOQ gene expression in adipose tissue was on average 2.8 times lower than in the comparison group (2.34 and 0.81 units, respectively, p < 0.05).

Conclusion. Analysis of the expression profiles of genes encoding key adipocytokines and of the functional and metabolic characte­ristics of visceral adipose tissue appears promising for identifying diagnostic and prognostic markers of MS and associated diseases.

Current evidence convincingly supports the key role of mast cells in triggering pro-inflammatory reactions, and of fibroblasts in tissue regeneration during the resolution phase of inflammation. Nevertheless, questions concerning their synergy during the acute phase of the inflammatory response — including the influence of acute-phase proteins on intercellular communication — remain poorly studied. In this work, using flow cytometry and quantitative fluorescence-based assessment of cell adhesion, we demonstrate that stimulation of Fcγ receptors on HMC-1 mast cells with specific ligands (C-reactive protein, aggregated immunoglo­bulin G, and serum amyloid P component) enhances the adhesive properties of these cells toward stromal elements — fibroblasts and the extracellular matrix. Notably, native HMC-1 mast cells did not show a secretory response to C-reactive protein sti­mulation in the form of histamine release. The ability to trigger a degranulation response with histamine release upon contact with C-reactive protein was associated with the expression of high-affinity FcγRI receptors, induced on the mast cell membrane by IFNγ. These findings reveal new aspects of the regulation of intercellular inte­ractions under conditions of acute inflammation, highlighting the role of cytokine modulation in the effector functions of immunocompetent cells.

Glycogen storage disease type Ib is a rare inherited metabolic disorder characterized by a combination of severe metabolic abnormalities and immune dysfunction. This article presents a clinical case of a pediatric patient with glycogen storage disease type Ib, complicated by chronic neutropenia, recurrent infectious and inflammatory skin lesions, and signs of immune dysregulation. A comprehensive clinical, laboratory, instrumental, and immunological assessment was performed, including evaluation of neutrophil functional activity, lymphocyte immunophenotyping, mitochondrial activity analysis, and assessment of the NF-κB signaling pathway. The findings demonstrate the systemic nature of immune alterations in GSD Ib and highlight the clinical relevance of extended immunological monitoring in affected patients.

Endometriosis and uterine fibroids are hormone-dependent gynecological disorders whose pathogenesis is closely associated with chronic inflammation and impaired immune regulation.

Aim — to determine the pattern of changes in the serum cytokine profile in women with endometriosis, intramural uterine fibroids, and their combination.

Materials and methods. The study included 88 women of reproductive age divided into four groups. Serum levels of IL-2, IL-6, IL-8, and IL-10 were measured using enzyme-linked immunosorbent assay.

Results. A cytokine imbalance was identified in patients with endometriosis and uterine fibroids, characterized by decreased IL-2 levels and increased pro-inflammatory mediators. The most pronounced alterations were observed in the combined pathology, with maximal elevations of IL-6 and IL-8 accompanied by a marked reduction in IL-2 and IL-10.

Conclusion. The findings indicate a leading role of immunoinflammatory dysregulation in the pathogenesis of these conditions and highlight the clinical and pathogenetic relevance of assessing the serum cytokine profile.

Immunotherapy is a powerful clinical strategy for the treatment of malignant tumours. The number of approved immuno-oncology drugs is growing, and many new therapeutic ap-proaches are currently at the stages of clinical and preclinical trials. Despite these ad-vances, a key challenge for the widespread use of immunotherapy remains the difficulty of controlled activation of the immune system. Existing approaches may cause serious side effects, including autoimmune reactions and nonspecific inflammation. In this regard, understanding the mechanisms that can increase the proportion of patients who respond to the therapy is a crucial factor both for improving treatment efficacy and for controlling its side effects.

The aim of this research is to examine and summarize data on the prognostic and predictive significance of biomarkers associated with the efficacy and safety of immunotherapy in malignant tumours. The study examines molecular genetic alterations (including circulat-ing tumour DNA), cancer-testis antigens, the PD-1 protein and its ligands, as well as ter-tiary lymphoid structures. Special attention is given to biomarkers of systemic and local responses. It has been shown that the cellular composition of the tumour microenvironment and peripheral blood is associated with disease prognosis, while levels of cytokines and soluble immune factors may predict the effectiveness of immunotherapy and the likelihood of side effects. The article also discusses delayed-type hypersensitivity reactions and modern methods for detecting biomarkers, which are used to evaluate the specific anti-tumor immune response.

The authors conclude that the most promising direction is the simultaneous analysis of multiple types of biomarkers using modern computational methods. This approach may improve the effectiveness and safety of immunotherapy and facilitate a transition to per-sonalized treatment.

Cell-free DNA (cfDNA) from animals and humans possesses immunomodulatory properties, and the underlying me­chanism of its action may involve binding to pattern recognition receptors such as TLR9. Activation of these receptors initiates inflammation and increases the production of proinflammatory cytokines. It is therefore relevant to study the effect of TLR9 receptor activation by the specific agonist ODN 1826 on changes in blood cfDNA levels and TNF-α production in response to an exogenous proinflammatory stimulus in C57BL/6 and Balb/c mice — strains known to differ in their response to the development of inflammation.

It was found that administration of the TLR9 receptor agonist ODN 1826 increased inflammation intensity in LPS-treated mice, as characterized by increased TNF-α and cfDNA concentrations in the blood and a decrease in the content of cfDNA covalently bound to proteins on the cell surface. At the early stage of inflammation development, the response of Balb/c mice to LPS was not qualitatively different from that of C57BL/6 mice.

These results suggest that agents capable of activating TLR9 may prove to be effective pharmacological tools for the treatment of immunopathological processes requiring correction of the Th1/Th2 balance.

For the first time, a comprehensive in vivo evaluation of the effects of long-term (45 days) daily intragastric administration of water solution of naturally occurring small molecules of chelidonic acid (ChA) to Balb/c mice was conducted. The study was focused on the morphofunctional state of several key organs involved in xenobiotic metabolism and excretion, including the stomach, liver, kidneys, as well as an immunocompetent organ (spleen). The obtained results demonstrate the absence of pathological changes in these organs when the substance was administered orally at a concentration of 10 mg/ kg in 0.2 ml of solvent (distilled water) for 45 days. Moreover, as previously established, ChA and its calcium salt at the indicated dose exhibit specific (osteogenic) activity against mesenchymal stromal/stem cells both in vitro and in vivo. These findings indicate an absence of general toxicity to studied organs of a low concentration of ChA in lineage mice, suggesting that it may be a promising candidate for future clinical use. This opens up promising opportunities for further research and development of an active pharmaceutical substance that is entirely domestic in origin. This is of great importance for the advancement of the field of regenerative biomedicine, primarily in the area of bone tissue engineering.

Elucidating the role of periodontopathogenic microor­ganisms in inflammatory periodontal diseases and the immune response they trigger in the pathogenesis may open up new op­portunities for the diagnosis, prevention, and treatment of this pa­thology.

The aim is to analyze the relationships between the taxonomic fea­tures of the microbiome of the gingival sulcus/periodontal pocket contents and immunological indicators in patients with gingivitis and chronic generalized periodontitis (CGP) of varying severity.

Materials and methods. The 16S rRNA gene was sequenced ac­cording to the Illumina protocol to determine the species compo­sition of the microbiome in the gingival sulcus and periodontal pocket of 84 patients. The concentration of pro- and anti-inflam­matory cytokines was determined in the selected samples using enzyme-linked immunosorbent assay. The peripheral blood of the patients was evaluated for the content of immunoglobulins A, M, and G and the phagocytic activity of neutrophils. Statistical data processing and correlation analysis were performed using the Sta­tistica 10 software package.

Results and discussion. It was found that patients with inflam­matory periodontal diseases had increased levels of IL-2, TNFα, and IL-4 in their oral fluid, as well as sIgA, while there was a sta­tistically significant decrease in the levels of IL-6 and IL-10. In the peripheral blood of patients with CGP, there was a decrease in the phagocytic activity of leukocytes and dysgammaglobulinemia. A significant “positive” correlation was found between the presence of representatives of the V. dispar species in the oral microbiome and increased levels of TNFα, IL-2, IL-4, and sIgA (τ = 0.27...0.36, p < 0.05), as well as a negative correlation between the occurrence of F. nucleatum, T. forsythia, and F. alocis with a number of immunological parameters — TNFα, IL-2, IL-4, sIgA, IgA, IgM, IgG (τ = – 0.57... – 0.86, p < 0.01).

Conclusion. The presence of P. gingivalis, F. nucleatum, F. alocis, and V. dispar in the oral microbiome of patients with chronic ge­neralized periodontitis contributes to the suppression of cellular and humoral immunity and is a potential biomarker of severe and progressive disease, which should be taken into account during comprehensive therapy.