Progesterone suppresses the fetal inflammatory response ex vivo.
OBJECTIVE
Progesterone supplementation has been shown to be efficacious in preventing preterm birth. We sought to investigate the effects of progesterone on fetal inflammatory responses.


METHODS
Fetal mononuclear cells were isolated from umbilical cord blood and exposed to vehicle or progesterone (P4) for 1 hour prior to lipopolysaccharide (LPS) stimulation. Supernatants were assayed for tumor necrosis factor-alpha. Similar experiments were performed using cyclic adenosine monophosphate (cAMP) and progesterone modulators. The effect of P4 treatment on intracellular cAMP levels was also determined.


RESULTS
LPS treatment led to a significant increase in cytokine production by fetal mononuclear cells. Despite the lack of detectable nuclear progesterone receptors, P4 suppressed this inflammatory response. R5020 (progesterone agonist), forskolin (cAMP inducer), and dibutyryl cAMP (cAMP agonist) all achieved immunosuppression. The cAMP antagonist, Rp-cAMP, blocked the inhibitory effect of progesterone. P4 significantly increased intracellular cAMP levels.


CONCLUSIONS
Progesterone rapidly suppresses the fetal inflammatory response, possibly via nongenomic activation of the cAMP cascade.
Schwartz
Nadav
N
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Xue
Xiangying
X
Elovitz
Michal A
MA
Dowling
Oonagh
O
Metz
Christine N
CN
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005333:Fetus / Q000166:cytology / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000196:embryology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D000242:Cyclic AMP