Leukemia Inhibitory Factor (LIF) induction in a model of septic pregnancy loss elicited by LPS

AISEMBERG J; VERCELLI C; BILLI S; FRANCHI AM

Los Cocos, Córdoba, Argentina

Congreso; III Latin-American Symposium Materno-Fetal Interaction & Placenta: Basic & Clinical Research; 2007

Leukemia inhibitory factor (LIF) induction in a model of septic pregnancy loss elicited by LPS. Aisemberg J., Vercelli C., Billi S., Franchi AM. Center for Pharmacological and Botanical Studies Buenos Aires, Argentina LPS administration to 7 day pregnant mice produced 100% of embryonic resorption after 24 h but it doesn´t affect the mother for future pregnancies. Endotoxin injection resulted in enhanced signs of sepsis and increased pro-inflammatory molecules production at implantation sites. Progesterone (P4) promotes allograft tolerance inducing the expression of immunomodulatory proteins in women undergoing normal pregnancies. LIF is a secreted cytokine with pleiotropic functions which include maternal tolerance. The aim of this work was to characterize LIF mRNA production and the possible modulation of LIF and pro-inflammatory mediators by P4. Balb/c females were injected with LPS (1 mg/g) at day 7 of pregnancy. After 6 h uterine and decidual tissues were removed to determine LIF mRNA levels (RT-PCR). Serum P4 levels were quantified (RIA). Prostaglandin E (PGE), NO and TNFa were determined in supernatant of tissues cultured with P4 for 48 h.  Females treated with LPS showed lower levels of serum P4 compared to control (p<0.01). LIF mRNA expression in LPS-treated mice was significantly higher (p<0.01) than in control group. P4 co-incubation increased LIF mRNA expression in control pregnant mice (p<0.01) suggesting that P4 up-regulated LIF expression in normal conditions. But when LIF mRNA expression was increased by LPS, P4 blocked the effect of LPS(p<0.001). We also found PGE, NO and TNFa synthesis augmented by LPS and that this effect was abrogated by P4. Even it was reported that estrogen stimulates LIF expression, it is the first time that it is demonstrated that progesterone modulates the murine LIF expression. These results suggest that low levels of P4 during inflammmation may contribute to the inflammatory disorder that concludes in embryonic resorption. Presentation modality: Poster Keywords: LIF, Embryonic Resorption, Sepsis.