IL-6 REGULATES INSULIN RESISTANCE AND CARDIOVASCULAR DISEASE DURING TRYPANOSOMA CRUZI EXPERIMENTAL INFECTION

Congreso; CONGRESS ON BIOSCIENCE; 2017

Sociedades Científicas de Argentina

Oxidative stress generation is proposed as the common pathogenic factor mediating the appearance of insulin resistance while producing increased cardiovascular risk. We have recently reported a potent anti-oxidant effect of IL-6, so we hypothesize that IL-6 could be involved in insulin sensitivity and cardiovascular function during T. cruzi infection. We observed that infection induces increased frequency of nitric oxide (NO)-producing monocytes in peripheral blood from IL-6-deficient mice (KO) in comparison with C57BL/6 (WT) mice at all days post-infection (dpi) studied (0 dpi p=0.0301, 4 dpi p=0.0006, 14 dpi p=0.0007, 21 dpi p=0.0165). Among the metabolic parameters assayed in plasma, we observed increased glucose (p=0.0120) and insulin (p=0.0286) levels, with the consequent augmented HOMA-IR index (p=0.0197) at 14 dpi in KO mice compared to WT mice. These results suggest that IL-6-deficiency induces acute insulin resistance. The fatty acid transporter and scavenger receptor CD36 is implicated in the pathogenesis of insulin resistance and associated cardiovascular complications. Considering that KO mice showed higher frequency of CD36+ circulating monocytes (p=0.0045) in comparison with WT mice at 14 dpi, we analyzed if IL-6 could be regulating insulin sensitivity by modulating this scavenger receptor. IL-6 stimulation of T. cruzi-infected bone marrow-derived macrophages (BMDM) diminished the frequency of CD36+ BMDM and increased the percentage of insulin receptor+ BMDM compared to unstimulated-infected cells. Considering that cardiovascular dysfunction is a complication of metabolic syndrome, we observed that KO mice showed increased creatin-kinase (CK) MB/total CK ratio (p=0.0016) and creatinine plasmatic levels (p=0.0003), biomarkers of cardiac and kidney damage respectively, in comparison with WT mice. Altogether, the data obtained show that IL-6 protects mice from T. cruzi-induced oxidative stress and the consequent insulin resistance and kidney dysfunction.