Study of the immune response and metabolism state using experimental models of hyperlipidemia and metabolic syndrome

• Tatiana N. Nikolaeva
• Vyacheslav V. Kozlov
• Tatiana N. Kozhevnikova
• Ekaterina A. Grigorieva
• Olga Yu. Sosnovskaya
• Sergey B. Cheknev
• Aleksander V. Sanin
• Alexander V. Pronin

Abstract

Introduction. The immune system plays an important role in the pathogenesis of hyperlipidemia (HL) and metabolic syndrome (MS). Metabolic dysfunctions are accompanied by disorders of cooperation, intercellular interaction of various parts of the immune system. The key pathogenetic factors of GL and MS are changes in the secretion of adipocyte mediators (adiponectin, leptin), pro-inflammatory and anti-inflammatory cytokines (CT). The data of experimental and clinical studies indicate the relationship and interdependence of cellular immune responses, mediators of intercellular interactions and metabolic disorders of the macroorganism.

The aim of this study was to estimate the population composition of spleen lymphoid cells, the production of cytokines and the functional activity of lymphocytes in 2 experimental models of MS and HL.

Material and methods. Experiments were performed on C57Bl/6 mice. The studies were carried out on two experimental models of MS and GL, based on long-term feeding of animals with a 20 % aqueous solution of fructose with the addition of cholesterol to the food and intraperitoneal administration of Poloxamer 407 to mice, respectively. The subpopulation composition of mice spleen cells was assessed by flow cytometry. Determination of leptin, adiponectin, insulin, cytokines interleukin(IL)-15, IL-22 in the blood serum of mice was performed by ELISA using commercial kits. The proliferation of lymphocytes was evaluated in the blast-transformation assay (RBTL).

Results. The results of the experiments carried out in the MS and HL models indicate a change in the population composition of the spleen (a decrease in CD4⁺- and CD8⁺-T cells numbers, activation of CD4⁺CD25⁺Foxp3⁺-Treg cells), accompanied by a decrease in the functional activity of immunocompetent T cells and an increase in the proliferative activity of B-lymphocytes. Also a violation of the production of IL-15 and IL-22, involved in lipid metabolism and dysfunctional changes in the mediators of lipid and carbohydrate metabolism (adiponectin, leptin, insulin) was observed, which in turn may serve as a prerequisite for the development of chronic inflammation, considered as the most important pathogenetic sign of MS.

Conclusion. Our experimental data on changes in the immune response and the state of metabolism confirm the feasibility of searching and screening for immunocorrection drugs intended for the prevention and treatment of hyperlipidemia and the MS symptom complex, based on a targeted effect on the leading steps in the pathogenesis of metabolic disease.

Keywords:metabolic syndrome; hyperlipidemia; adiponectin; leptin; experimental model; immune response; Treg cells; cytokines

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