Effect of progesterone on proinflammatory cytokine production by monocytes stimulated with pathogens associated with preterm birth

Problem A number of clinical trials have demonstrated that supplemental progesterone (P-4) can prevent preterm birth. Although P-4 can decrease the production of mediators of inflammation by lipopolysaccharide (LPS)-stimulated macrophages, a majority of infections associated with preterm birth are due to Ureaplasma urealyticum, which does not contain LPS. Therefore, we studied whether P-4 could lower the production of proinflammatory cytokines by monocytes stimulated with U. urealyticum. Method of study Human monocytes (THP-1 cells) were treated with P-4 and then stimulated with heat-killed Escherichia coli or U. urealyticum. Cytokine concentrations in the conditioned medium were then measured by ELISA and relative viability of the cells was assessed colorimetrically. The impact of P-4 on interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF-alpha) and IL-8 production was assessed by comparing levels across different P-4 dosages and organism concentrations. Results Both organisms increased IL-1 beta, TNF-alpha and IL-8 production in a dose-dependent manner. P-4 enhanced the production of IL-1 beta and IL-8, but inhibited TNF-alpha production by monocytes stimulated with either organism. Conclusion P-4 modulates cytokine production by E. coli and U. urealyticum-stimulated monocytes in a similar manner and is not strictly immunosuppressive. This suggests that P-4 does not prevent preterm birth by simply suppressing bacteria-stimulated cytokine production.