In the search to identify differences in the immunological response between patients with the indeterminate or cardiac form of Chagas disease, trypomastigote-specific peripheral blood mononuclear cell (PBMC) proliferative responses were studied. Suppression of lymphoproliferation occurred in both groups of patients, being more intense in those with the cardiac form. By adding to the cultures neutralizing mAbs anti-IFN-gamma, anti-IL-4, anti-IL-13, or anti-IL-10, indomethacin to block prostaglandin synthesis, NMMA as inhibitor of nitric oxide (NO) synthesis, or glutathione-peroxidase as H(2)O(2) scavenger, it was found that indomethacin augmented lymphoproliferation in both groups of patients. However, anti-IL-10 treatment increased proliferation only in PBMC cultures from patients with the cardiac form, indicating that in these patients, IL-10 was suppressing the immune response. These patients also had higher IL-10 levels in unstimulated cultures and higher PGE(2) levels in stimulated cultures. The results evidence that IL-10 regulates parasite-specific T cell responses in patients with the cardiac form, whereas regulation by prostaglandins (PG) occurs in patients with either cardiac or indeterminate form of the disease.