T-HELPER-1 RESPONSE AGAINST LEISHMANIA-MAJOR IN PREGNANT C57BL 6 MICEINCREASES IMPLANTATION FAILURE AND FETAL RESORPTIONS - CORRELATION WITH INCREASED IFN-GAMMA AND TNF AND REDUCED IL-10 PRODUCTION BY PLACENTAL CELLS/

Maternal immune responses can influence fetal survival and several cyt okines have harmful or protective effects on pregnancy. The Th1 cytoki nes IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show th e opposite pattern: resistance is associated with the preferential mou nting of a Th1 response, whereas a Th2 response exacerbates the diseas e. We therefore asked whether the curative Th1 response against Leishm ania major in genetically resistant C57BL/6 mice, would compromise con current pregnancy. The number of resorptions as assessed by uterine sc ars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 c ytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57B L/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short perio d early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced high er resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only p lacental maintenance but also preimplantation events.