414: Progesterone effect on lipoteichoic acid (LTA) induced secretion secretion of IL-6 in maternal and fetal mononuclear cells

Our objective is to determine whether progesterone can modulate response to lipoteichoic acid (LTA) induced IL-6 production in maternal and fetal mononuclear cells. Fetal cord blood was obtained from patients with uncomplicated term pregnancies undergoing scheduled cesarean sections. Maternal blood was obtained from women at 16-20 weeks gestation not exposed in vivo to exogenous progesterone. Mononuclear cells were isolated by Histopaque gradient, and were treated with LTA (50ug/mL), or P4 (30ng/mL) or pretreated with P4 and then exposed to LTA. Culture supernatants were collected and evaluated for secreted IL-6 by ELISA. Data was analyzed using Student’s t test, P value<0.05 significant. LTA, a cell wall component of group B streptococcus (GBS) bacteria, induces IL-6 secretion. In fetal mononuclear cells, a 2-fold increase in IL-6 production occurs with exposure to LTA. Secretion of IL-6 is significantly blocked by pre-treatment with progesterone (p=0.0005). In maternal mononuclear cells, IL-6 secretion had a 35-fold increase with exposure to LTA; however it P4 pre-treatment failed to block response to LTA. In this in vitro model, we found that LTA induced production of IL-6 can be modulated by pre-treatment with P4 in fetal, but not maternal, mononuclear cells. We previously demonstrated that P4 can inhibit IL-6 secretion in maternal and fetal mononuclear cells. LPS effects are mediated through the Toll-like Receptor 4 (TLR4). Similarly, other toll like receptor family members (TLR 2/6) can be activated by LTA to produce pro-inflammatory cytokines. Current studies suggest that only one third of patients respond to exogenous progesterone therapy for the prevention of preterm birth. We postulate that the discrepancy in maternal mononuclear cell response to LPS versus LTA may play a role in host response to exogenous progesterone therapy.