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

SANMARCO LM; EBERHARDT N; PONCE N; BERGERO G; VIGLIANO C; CANO R; AOKI P

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínico

Oxidative stress generation is proposed as the common pathogenicfactor 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 frequencyof nitric oxide (NO)-producing monocytes in peripheral bloodfrom 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 metabolicparameters assayed in plasma, we observed increased glucose(p=0.0120) and insulin (p=0.0286) levels, with the consequent augmentedHOMA-IR index (p=0.0197) at 14 dpi in KO mice comparedto WT mice. These results suggest that IL-6-deficiency inducesacute insulin resistance. The fatty acid transporter and scavengerreceptor CD36 is implicated in the pathogenesis of insulin resistanceand 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 dysfunctionis 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.