Does Progesterone Alter Toll-Like Receptor-Stimulated Monocyte Production of Cytokines?
OBJECTIVE: Current models for infection-mediated preterm birth suggest that bacteria stimulate the production of proinflammatory cytokines and cause the fetus to lose its immunological privileges. Pharmacological levels of progesterone (P4) have been proposed to inhibit preterm birth by suppressing such immune reactions that lead to rejection of the fetal allograft. Bacteria stimulate the production of proinflammatory cytokines through interactions with the Toll-Like Receptors (TLRs). We studied whether P4 alters TLR-2 and TLR-4 agonist-stimulated IL-1b and TNF-a production by human monocytes in vitro. STUDY DESIGN: Human monocytes (THP-1 cells) were plated and preincubated overnight. Progesterone was added at increasing doses of 0 to 10 mg/ ml and incubated for 24 h. Cells were then stimulated with 0 to 8 mg/ml Pam3Cys (a TLR-2 agonist), 0 to 10 mg/ml Lipopolysaccharide (LPS, a TLR-4 agonist) or 0 to10 mg/ml Lipid A (a TLR-4 agonist) for an additional 24 h. Concentrations of IL-1b and TNF-a in the conditioned medium were then quantified by ELISA. Each experiment was replicated three times. RESULTS: For monocytes stimulated with 1 mg/ml Pam3Cys, 1 mg/ml LPS, or 1 mg/ml Lipid A, pre-treatment with 10 mg/ml P4 inhibited the production of TNF-a but enhanced the production of IL-1b. Progesterone at this superphysiological concentration also inhibited the dose-dependent rise in TNF-a production but enhanced the dose-dependent rise in IL-1b production caused by each TLR agonist. CONCLUSION: High levels of P4 inhibit the production of TNF-a but increase the production of IL-1b by monocytes stimulated with TLR-2 or TLR-4 agonists. These results suggest that any potential immunomodulatory effects of P4 are similar for TLR-2 and TLR-4 mediated inflammation.
Published In/Presented At
Peltier, M. Smulian, J. C. (2006). Does Progesterone Alter Toll-Like Receptor-Stimulated Monocyte Production of Cytokines? Am J Obstet Gynecol 2005;193(S60):Abstract #178. Poster Presented at: The 26th Annual Meeting of the Society for Maternal-Fetal Medicine. Miami, Florida.
Obstetrics and Gynecology
Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology Faculty