Chronic Chagas' disease cardiomyopathy patients display an increased IFN-gamma response to Trypanosoma cruzi infection

One-third of all Trypanosoma cruzi-infected patients eventually develop chr onic Chagas' disease cardiomyopathy (CCC), a particularly lethal inflammato ry dilated cardiomyopathy, where parasites are scarce and heart-infiltratin g mononuclear cells seem to be the effectors of tissue damage. Since T cruz i is a major inducer of interleukin-12 production, the role of inflammatory cytokines in the pathogenesis of CCC was investigated. We assayed cytokine production by peripheral blood mononuclear cells (PBMC) from CCC and asymp tomatic T cruzi-infected (ASY) individuals, as well as by T cell lines from endomyocardial biopsies from CCC patients. PBMC from CCC and ASY patients produced higher IFN-gamma levels than normal (N) individuals in response to B13 protein and phytohaemagglutinin PHA; IFN-gamma high responders (greate r than or equal to1 ng/ml) were 2-3 fold more frequent among CCC patients t han ASY individuals. Conversely, IL-4 production in response to the same st imuli was suppressed among T. cruzi-infected patients. The frequency of PHA -induced IFN gamma -producing cells on PBMC was significantly higher among CCC than ASY and N individuals. IFN-gamma and TNF-a were produced by ten ou t of ten PHA-stimulated T cell lines from CCC patients; IL-2 and IL-10 were produced by four out of ten and one out of ten lines, respectively; IL-4, IL-1 alpha, IL-1 beta, IL-6 and IL-12 were undetectable. Our results sugges t that CCC and ASY patients may respond differentially to the IFN-gamma -in ducing stimulus provided by T. cruzi infection. Given the T-1-type cytokine profile of heart-infiltrating T cell lines from CCC patients, the ability to mount a vigorous IFN-gamma -response may play a role on the differential susceptibility to CCC development. (C) 2001 Academic Press.