IL-10 PREVENTS NATURALLY-OCCURRING FETAL LOSS IN THE CBA X DBA 2 MATING COMBINATION, AND LOCAL DEFECT IN IL-10 PRODUCTION IN THIS ABORTION-PRONE COMBINATION IS CORRECTED BY IN-VIVO INJECTION OF IFN-TAU/

CBA x DBA/2 placentae are quantitatively or qualitatively deficient in their production of the anti-inflammatory Th2-type cytokines IL-4 and IL-10 compared with the nonresorption-prone CBA x BALB/c mating combi nation. Wastage in this mating combination is accompanied by increased levels of local inflammatory cytokines. In addition, alloimmunization enhances the placental production of IL-4 and IL-10 in CBA x DBA/2 ma tings. Furthermore, rIL-10 by itself completely reverses the high inci dence of fetal resorption after i.p. injection. Conversely, anti-IL-10 increases the resorption rate, but only in CBA x DBA/2 matings. On th e other hand, injecting either anti-IFN-gamma or pentoxifillin (an ant i-TNF agent) partially reduces the resorption. When given together, th ey produce a synergistic remission of fetal loss. Finally, we report t hat recombinant ovine trophoblast protein, an IFN-tau which is known t o influence reproductive outcome in ruminants, can also counteract inc reased CBA x DBA/2 fetal resorption. It simultaneously induces increas ed placental IL-4 and IL-10 production in this mating combination. The se results indicate that the placentally produced anti-inflammatory cy tokines can play a vital role in the survival to term of the fetal all ograft, by counteracting deleterious inflammatory cytokines.