Synergy of Lipopolysaccharide and Inflammatory Cytokines in Murine Pregnancy: Alloimmunization Prevents Abortion but Does Not Affect the Induction of Preterm Delivery

Abstract

Partial resorption or abortion (depending upon the stage of gestation) can be induced with lower doses of lipopolysaccharide (LPS) (DIFCO) and human R-TNF than previously demonstrated. As can be expected, the abortion-prone CBA X DBA/2 and B10 X B10.A mating combinations are the most sensitive to such low doses. LPS synergizes with low doses of IL-2, gamma interferon, poly(I) · poly(C) I2U. Treatment by GM-CSF, IL-3, or anti-natural killer antiserum decreases both TNF levels and abortion rates. Similar prevention of induced resorptions are obtained with either a neutralizing polyclonal rabbit anti-TNF antiserum or with pentoxyfilline, which has been shown to reduce resorption rates in CBA X DBA/2 pregnancies. More important, abortions induced by low doses of LPS or R-TNF can be prevented by alloimmunization. During late gestation, on the contrary, LPS- or TNF-induced delivery cannot be counteracted by alloimmunization nor by a progesterone-induced blocking factor, at least in the regimens employed by us. Therefore, although resorptions and parturition share common pathways consisting of immune mediators, they are not regulated similarly by the maternal immune system.