IL-6/STAT3 and adipokine modulation using tocilizumab in rats with fructose-induced metabolic syndrome

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2020-12, Vol.393 (12), p.2279-2292
• Main Authors: Yahia, Haneen, Hassan, Azza, El-Ansary, Mona R., Al-Shorbagy, Muhammad Y., El-Yamany, Mohamed F.
• Format: Article
• Language: English
• Subjects: Adiponectin; Biomedical and Life Sciences; Biomedicine; Blood pressure; Body weight gain; Cytokines; Drinking water; Dyslipidemia; Environmental factors; Etiology; Fructose; Immunosuppressive agents; Insulin; Interleukin 6; Leptin; Metabolic syndrome; Monoclonal antibodies; Neurosciences; Original Article; Pharmacology/Toxicology; Rodents; Stat3 protein
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-020-01940-z

Metabolic syndrome (MetS) is a low-grade inflammation state that results from an interplay between genetic and environmental factors. The incidence of MetS among individuals with insulin resistance, dyslipidemia, elevated blood pressure, and obesity, which constitute the syndrome, is 40% in the Middle East. The absence of an approved therapeutic agent for MetS is one reason to investigate tocilizumab (TCZ), which might be effective in the treatment of MetS. Results have implicated interleukin 6 (IL-6) in the development of MetS, identifying inflammation as a critical factor in its etiology and offering hope for new therapeutic approaches development. Here, we evaluate whether tocilizumab can be used for metabolic syndrome treatment. We assigned rats to three groups, 8 rats each: a negative-control group, provided with standard rodent chow and water; a fructose-fed group, provided with standard rodent chow and 10% fructose in drinking water for 22 weeks; and a treatment group, fed as per the metabolic syndrome group but treated with tocilizumab (5 mg/kg/week, intraperitoneal) for the final 5 weeks. Treatment with TCZ successfully ameliorated the damaging effects of fructose by stabilizing body weight gain and through the normalization of serum biochemical parameters and histopathological examination. Significant differences in adipokine levels were perceived, resulting in a significant decline in serum leptin and interleukin 6 (IL-6) levels concurrent with adiponectin normalization. Tocilizumab might be an effective agent for the treatment of metabolic syndrome. However, further investigations on human subjects are needed before the clinical application of tocilizumab for this indication.