CORRELATION BETWEEN PROINFLAMMATORY MEDIATORS AND VENTRICULAR DYSFUNCTION IN AN EXPERIMENTAL MODEL OF CHAGAS DISEASE IN IL10 KO MICE

DONATO, MARTIN; PIERALISI, AZUL VICTORIA; GELPI, RICARDO; RADA, MARÍA JIMENA; PENAS, FEDERICO NICOLÁS; MASCOLO, PAULA; GOREN, NORA BEATRIZ; ALBA SOTO, CATALINA; CEVEY, ÀGATA CAROLINA; MIRKIN, GERARDO A.

VIRTUAL

Congreso; Reunión Anual de Sociedades de Biociencia 2020. SAIC-SAI-SAFIS; 2020

Sociedad Argentina de Investigación Clínica

Chagas disease, caused by Trypanosoma cruzi (Tc) infection, isconditioned by parasite persistence and the development of an inflammatory response. Interleukin 10 (IL10) is a pleiotropic cytokineinvolved in the regulation of inflammatory processes. In previousworks we showed that Fenofibrate (Fen), a PPARα synthetic ligand,modulates inflammation and restores cardiac function in T. cruzi -infected wild type mice. Furthermore, infection of IL10 knockout mice(IL10 KO) with the K98 clone of CA-I Tc strain triggered ventriculardysfunction and the increase of expression and concentration ofproinflammatory mediators. Fen treatment inhibited the expressionand release of inflammatory mediators and restored the ventricularfunction. Taking this into account, we considered to analyze the correlation between various proinflammatory mediators and ventricularfunction. Using Spearman correlation test, we observed that thereis a strong correlation between the increased mRNA expressionof IL6, NOS2, TNFα and TGFβ in cardiac tissue, as well as withthe increase in plasma concentration of IL6, TNFα, and IL17 withthe decrease in the percentage of both Ejection Fraction (EF) andShortening Fraction (SF) in Tc-infected IL10 KO mice. The strongestcorrelations were observed between the concentration of IL6 (r=-1)and TNFα (r=-0.94), and expression of TGFβ mRNA (r=-0.95) withboth EF and SF. Treatment with fen inhibits the expression and release of these mediators, thus improving ventricular function. This isevidenced by the decrease in the correlation between these proinflammatory mediators, and both EF and SF. Meanwhile, no associations were found between the studied parameters in WT mice,since infection did not cause ventricular dysfunction. These resultssuggest a strong correlation between expression and release ofproinflammatory mediators and ventricular dysfunction caused byK98 infection in IL10 KO mice