Study of the possible effects of IL-6 antagonist tocilizumab on experimentally induced metabolic syndrome in rats / Haneen Yahia Mohammed ; Supervised Hossam M. M. Arafa , Mohamed F. Elyamani , Mohammad Y. Elshorbagy

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Metabolic Syndrome is a state of chronic low grade inflammation as a consequence of complex interplay between genetic and environmental factors. Insulin resistance, visceral adiposity, atherogenic dyslipidemia, endothelial dysfunction, genetic susceptibility, elevated blood pressure and obesity are amongst the several factors, which constitute the syndrome. Fructose overload has been well established as a model of metabolic syndrome since it shares many facets of the features encountered in the syndrome. In the current study, animals were challenged with fructose 10% in drinking water for 18 weeks. Fructose overload induced insulin resistance, hypertriglyceridemia, hypercholesterolemia, body weight gain, increased systolic blood pressure as well as deterioration in liver and kidney function tests. Oxidative stress and dysregulation of a host of adipokines were also observed. Tocilizumab is a monoclonal recombinant human antibody that acts as an interleukin-6 (IL-6) receptor antagonist. Studies indicate that it suppresses inflammation via IL-6 receptors. Currently, tocilizumab is approved to treat inflammatory diseases such as rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, and the systemic form of juvenile rheumatoid arthritis. Due to its reported anti-inflammatory effects and the notion that metabolic syndrome in rheumatoid arthritis patients prevails, this warranted the attention to address the potential therapeutic effects of tocilizumab. The monoclonal antibody, administered in a weekly dose of 5 mg/kg, IP for 5 weeks, improved almost all the cardiometabolic derangements induced by fructose overload. Its observed antioxidant and anti-inflammatory effects via modulation of interlukin-6, leptin and adiponectin may account at least partly for the mechanisms whereby tocilizumb improved this experimental paradigm of metabolic syndrome. One could conclude that tocilizumab may have beneficial effects in metabolic syndrome particularly that associated with rheumatoid arthritis

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