Congresos y reuniones científicas
Título:
IL-6 regulates insulin resistance and cardiovascular disease during Trypanosoma cruzi experimental infection
Autor/es:
SANMARCO, LM; EBERHARDT, N; PONCE, NE; BERGERO, GASTÓN; VIGLIANO, C; CANO, RC; AOKI, MP
Reunión:
Congreso; Reunión conjunta de Sociedades de Biociencias; 2017
Resumen:
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. cruziinfection. 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