IL-6 regulates insulin resistance and cardiovascular disease during Trypanosoma cruzi experimental infection

NICOLÁS ERIC PONCE; ROXANA CAROLINA CANO; NATALIA EBERHARDT; CARLOS VIGLIANO; LILIANA MARIA SANMARCO; GASTÓN BERGERO; MARIA DEL PILAR AOKI

Buenos Aires

Congreso; I Reunión de Biociencias; 2017

Sociedad Argentina de Inmunología

Oxidative stress generation is proposed as the common pathogenic factor mediating the appearance of insulin resistance whileproducing increased cardiovascular risk. We have recently reporteda potent anti-oxidant effect of IL-6, so we hypothesize that IL-6 couldbe involved in insulin sensitivity and cardiovascular function duringT. cruzi infection. We observed that infection induces increased frequency of nitric oxide (NO)-producing monocytes in peripheral bloodfrom IL-6-defcient 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 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 comparedto WT mice. These results suggest that IL-6-defciency inducesacute insulin resistance. The fatty acid transporter and scavengerreceptor CD36 is implicated in the pathogenesis of insulin resistance and associated cardiovascular complications. Considering thatKO mice showed higher frequency of CD36+ circulating monocytes(p=0.0045) in comparison with WT mice at 14 dpi, we analyzed if IL-6could be regulating insulin sensitivity by modulating this scavengerreceptor. IL-6 stimulation of T. cruzi-infected bone marrow-derivedmacrophages (BMDM) diminished the frequency of CD36+ BMDMand increased the percentage of insulin receptor+ BMDM comparedto unstimulated-infected cells. Considering that cardiovascular dysfunction is a complication of metabolic syndrome, we observed thatKO mice showed increased creatin-kinase (CK) MB/total CK ratio(p=0.0016) and creatinine plasmatic levels (p=0.0003), biomarkersof cardiac and kidney damage respectively, in comparison with WTmice. Altogether, the data obtained show that IL-6 protects micefrom T. cruzi-induced oxidative stress and the consequent insulinresistance and kidney dysfunction.