IL-1b is not critical to chronic heart dysfunction in mice with Chagas disease

Long after Trypanosoma cruzi infection, 40% of individuals develop a

progressive chronic chagasic cardiomyopathy (CCC), with systolic

dysfunction and arrhythmias. Since we previously showed IL-1b mediates the

development of systolic dysfunction and cardiac arrhythmias in diabetes

mellitus and cardiorenal syndrome, and IL-1b remains elevated in Chagas

disease patients, here we tested the role of IL-1b in CCC using a mouse

model. Mice de cient in IL-1R expression (Il-1r−/−) survived acute T. cruzi

infection with greater parasitemia than controls but did not lose weight as

wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular

repolarization intervals (QJ), while Il-1r−/− presented intervals like noninfected

controls. Infected Il-1r−/− and WT did not differ in stroke volume (SV), the

incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart

action potential duration (APD), or the incidence of triggered activity after S1–

S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We

also treated chronically infected WT mice with an IL-1R antagonist, anakinra.

Treatment shortened the QJ interval but did not improve the SV or the

incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered

activity following the electrical extra-stimulation protocol. In conclusion, the

absence of functional IL-1b/IL-1R signaling did not prevent or reverse the

decrease of SV or the incidence of cardiac arrhythmias induced by chronic T.

cruzi infection, implying this is not a critical mechanism in generating or

maintaining CCC. Since similar cardiac abnormalities were previously

credited to IL-1b signaling, ruling out this mechanism is important to

discourage further attempts of IL-1b blockade as a therapeutical measure.