Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-gamma as important determinants ofchemokine mRNA expression during infection with Trypanosoma cruzi

We investigated the kinetics of parasite replication, leukocyte migration, and cytokine/chemokine mRNA expression in the heart tissue from animals inf ected with the Colombiana strain of Trypanosoma cruzi. Cardiac tissue paras itism was noticeable at 15 days, peaked around 30 days and was dramatically reduced at 120 days postinfection (p.i.), Kinetic studies showed that the inflammatory infiltrate was dominated by the presence of alpha beta T CD3() CD4(+) CD8(-), alpha beta T CD3(+) CD4(-)CD8(+) lymphocytes and macrophag es. The mRNA expression of the monokines IL-1 beta and IL-12(p40) was eleva ted at 15 days p,i. and controlled at later time points. In contrast, TNF-a lpha mRNA was expressed throughout the infection. Interestingly, we found t hat at 15 and 30 days p.i. cytokine expression was dominated by the presenc e of IFN-gamma mRNA, whereas at 60 days or later time points the balance of type 1 and type 2 cytokines was switched in favor of IL-4 and IL-10 mRNAs, The chemokine mRNAs encoding JE, MIP-l alpha, MIP-1 beta, KC, and MIP-2 we re all mainly expressed at 15 and/or 30 days p,i. and diminished thereafter . In contrast, the expression of RANTES, MIG and IP-10 mRNAs was augmented at 15 days p.i. and persisted at high levels up to 120 days p,i. Taken toge ther, our results indicate that regulation of IFN-gamma and chemokine expre ssion, associated with decreased tissue parasitism, may be largely responsi ble for the control of inflammation and immunopathology observed in the car diac tissue of animals infected with ir: cruzi. (C) 2000 Editions scientifi ques et medicales Elsevier SAS.