Cyclooxygenase is involved in the effects of progesterone-induced blocking factor on the production of interleukin 12

Objective: Immunologic effects of progesterone are mediated by the progesterone-induced blocking factor. Progesterone-induced blocking factor inhibits natural killer cytotoxic activity and arachidonic acid release from mononuclear cells. The relationship between increased prostaglandin synthesis and increased cytotoxic activity of the lymphocytes is still unclear; therefore we investigated the effect of progesterone-induced blocking factor–neutralizing antibody, as well as simultaneous indomethacin treatment, on interleukin 12 production. Study Design: Pregnancy lymphocytes were treated with anti–progesterone-induced blocking factor antibody or lipopolysaccharide as a positive control in the presence or absence of indomethacin. Interleukin 12 production by peripheral blood mononuclear cells was detected by immunocytochemical examination. The 2-tailed Student t test was used for statistical evaluation. Results: Neutralization of progesterone-induced blocking factor, as well as lipopolysaccharide treatment, resulted in an increased expression of interleukin 12 that was corrected by simultaneous indomethacin treatment. Conclusion: Progesterone-induced blocking factor reduces the expression of interleukin 12 via the inhibition of arachidonic acid metabolism. This results in lowered cytotoxic natural killer activity, which favors a normal pregnancy outcome. (Am J Obstet Gynecol 2000;183:126-30.)