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

SANMARCO LILIANA; EBERHARDT NATALIA; PONCE NICOLAS; BERGERO GASTÓN; VIGLIANO CARLOS; CANO ROXANA; AOKI PILAR

Congreso; Revista Medicina; 2017

Oxidative stress generation is proposed as the common pathogenic factormediating the appearance of insulin resistance while producing increasedcardiovascular 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 andcardiovascular function during T. cruzi infection. We observed that infectioninduces increased frequency of nitric oxide (NO)-producing monocytes inperipheral 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 dpip=0.0006, 14 dpi p=0.0007, 21 dpi p=0.0165). Among the metabolic parametersassayed 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 andscavenger receptor CD36 is implicated in the pathogenesis of insulin resistanceand associated cardiovascular complications. Considering that KO miceshowed higher frequency of CD36+ circulating monocytes (p=0.0045) incomparison with WT mice at 14 dpi, we analyzed if IL-6 could be regulatinginsulin sensitivity by modulating this scavenger receptor. IL-6 stimulation of T.cruzi-infected bone marrow-derived macrophages (BMDM) diminished thefrequency of CD36+ BMDM and increased the percentage of insulin receptor+BMDM compared to unstimulated-infected cells. Considering thatcardiovascular dysfunction is a complication of metabolic syndrome, weobserved that KO mice showed increased creatin-kinase (CK) MB/total CK ratio(p=0.0016) and creatinine plasmatic levels (p=0.0003), biomarkers of cardiacand kidney damage respectively, in comparison with WT mice. Altogether, thedata obtained show that IL-6 protects mice from T. cruzi-induced oxidativestress and the consequent insulin resistance and kidney dysfunction.