CYTOKINE PROFILES DURING EXPERIMENTAL CHAGAS-DISEASE

People infected with Trypanosoma cruzi remain so for life, yet only 30 -40% of these individuals develop characteristic chagasic cardiomyopat hies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T. cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-gamma in both mouse strains. However, the amount of IFN-gamma in supernatants from cultures of B10.D2 spleen cells initia ted during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Co n A-stimulated spleen cells from acute DBA/2 mice produced approximate ly twice as much IL-10 and significantly more IL-4 than cells from B10 .D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mic e, but when using cells from chronic DBA/2 mice, levels continued to i ncrease beyond the already high levels secreted by cells harvested dur ing the acute phase. Proliferative responses to Con A stimulation by s pleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest t hat enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoi mmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.