Hydroxyprogesterone caproate and progesterone increase tumor necrosis factor-alpha production in lipopolysaccharide stimulated whole blood from non-pregnant women.
OBJECTIVE
Hydroxyprogesterone caproate (17-P) and progesterone have been shown to decrease the rate of preterm birth in high-risk pregnant women, but the mechanism of action is unknown. We hypothesized that 17-P or progesterone would reduce production of the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), after lipopolysaccharide (LPS) stimulation of whole blood.


METHODS
Whole blood collected from 10 non-pregnant women in the follicular phase was treated with LPS (1000 ng/mL) alone or with either 17-P or progesterone (125 ng/mL and 1250 ng/mL) and LPS. Supernatant collected after 24 h was tested for TNF-alpha by enzyme immunoassay. Results were compared using the Wilcoxon rank sum test.


RESULTS
Whole blood treated with 17-P or progesterone in addition to LPS produced significantly higher TNF-alpha concentrations than blood treated with LPS alone.


CONCLUSIONS
17-P and progesterone appear to have a pro-inflammatory effect during LPS stimulation of blood from non-pregnant women in vitro. Our data suggest that the reduction in pre-term birth in women treated with progesterone is not mediated through an anti-inflammatory effect on peripheral blood cells.
Amory
Josephine
J
Department of Obstetrics and Gynecology, University of Washington Seattle, WA 98195, USA. jhamory@u.washington.edu
Lawler
Richard
R
Shields
Laurence
L
D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology / Q000517:prevention & control; D011374:Progesterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D006908:Hydroxyprogesterones; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000077713:17 alpha-Hydroxyprogesterone Caproate; D011374:Progesterone