Demonstration of an indomethacin-sensitive mechanism regulating immune reactivity in Chagas' disease patients.
We investigated some aspects of the regulation of the immune response that were sensitive to the effect of indomethacin, an inhibitor of prostaglandin synthesis, in two groups of patients in the chronic phase of Chagas' disease, and in normal controls. One group of patients was defined as being infected but with no clinical evidence of cardiac involvement, while the other showed electrocardiographic alterations that are characteristic of Chagasic cardiomyopathy. The in vitro responses to mitogens (phytohemagglutinin and concanavalin A) and Trypanosoma cruzi antigens were evaluated in the presence or absence of indomethacin. It was found that the in vitro mitogenic stimulation by both phytohemagglutinin and concanavalin A of peripheral blood mononuclear cells from normal controls and infected and cardiomyopathic patients was significantly increased by indomethacin. An inverse correlation was found between the initial response to concanavalin A and the subsequent increase caused by the presence of indomethacin, for both the patients and the controls. Considering specific responses to T. cruzi antigens, we showed that in the presence of indomethacin these were significantly increased in infected patients, but not in cases of cardiomyopathy. Again, a significant inverse correlation was found between the basal responsiveness and the indomethacin-induced change. In general, infected patients showed changes in the presence of indomethacin that were most comparable to those of normal individuals. It would appear, therefore, that normal indomethacin-sensitive (prostaglandin-dependent) suppressor mechanisms operate in Chagas' patients. In certain cardiomyopathy patients, however, these control mechanisms may not operate; a possible consequence of this could be tissue damage.
D000818:Animals; D014355:Chagas Disease / Q000276:immunology*; D002908:Chronic Disease; D003208:Concanavalin A; D005260:Female; D006801:Humans; D007213:Indomethacin; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D010835:Phytohemagglutinins; D012016:Reference Values; D014349:Trypanosoma cruzi / Q000276:immunology
D010835:Phytohemagglutinins; D003208:Concanavalin A; D007213:Indomethacin