title: Effect of progesterone on proinflammatory cytokine production by monocytes stimulated with pathogens associated with preterm birth.
abstract: OBJECTIVE
  A number of clinical trials have demonstrated that supplemental progesterone (P4) can prevent preterm birth. Although P4 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 P4 could lower the production of proinflammatory cytokines by monocytes stimulated with U. urealyticum.
  
  
  METHODS
  Human monocytes (THP-1 cells) were treated with P4 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 P4 on interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-8 production was assessed by comparing levels across different P4 dosages and organism concentrations.
  
  
  RESULTS
  Both organisms increased IL-1alpha, TNF-alpha and IL-8 production in a dose-dependent manner. P4 enhanced the production of IL-1beta and IL-8, but inhibited TNF-alpha production by monocytes stimulated with either organism.
  
  
  CONCLUSIONS
  P4 modulates cytokine production by E. coli and U. urealyticum-stimulated monocytes in a similar manner and is not strictly immunosuppressive. This suggests that P4 does not prevent preterm birth by simply suppressing bacteria-stimulated cytokine production.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA. peltiemr@umdnj.edu
authors.forename: Morgan R
authors.initials: MR
authors.lastname: Peltier
authors.forename: Siew C
authors.initials: SC
authors.lastname: Tee
authors.forename: John C
authors.initials: JC
authors.lastname: Smulian
mesh_terms: D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004926:Escherichia coli / Q000472:pathogenicity; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology* / Q000382:microbiology; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D016990:Ureaplasma urealyticum / Q000472:pathogenicity
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; D011372:Progestins; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone