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 combination. 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 matings. Furthermore, rIL-10 by itself completely reverses the high incidence of fetal resorption after i.p. injection. Conversely, anti-IL-10 increases the resorption rate, but only in CBA x DBA/2 matings. On the other hand, injecting either anti-IFN-gamma or pentoxifillin (an anti-TNF agent) partially reduces the resorption. When given together, they produce a synergistic remission of fetal loss. Finally, we report that recombinant ovine trophoblast protein, an IFN-tau which is known to influence reproductive outcome in ruminants, can also counteract increased CBA x DBA/2 fetal resorption. It simultaneously induces increased placental IL-4 and IL-10 production in this mating combination. These results indicate that the placentally produced anti-inflammatory cytokines can play a vital role in the survival to term of the fetal allograft, by counteracting deleterious inflammatory cytokines.
Chaouat
G
G
INSERM CJF 92 09, Antoine Béclére Hospital, Clamart, France.
Assal Meliani
A
A
Martal
J
J
Raghupathy
R
R
Elliott
J F
JF
Elliot
J
J
Mosmann
T
T
Wegmann
T G
TG
D000022:Abortion, Spontaneous / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D003656:Decidua / Q000166:cytology; D005260:Female; D005327:Fetal Resorption / Q000517:prevention & control; D007370:Interferon Type I / Q000096:biosynthesis / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D010431:Pentoxifylline / Q000494:pharmacology; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology
D007370:Interferon Type I; D007519:Isoantigens; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C020947:interferon tau; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010431:Pentoxifylline