THE IMMUNOLOGICAL PREGNANCY PROTECTIVE EFFECT OF PROGESTERONE IS MANIFESTED VIA CONTROLLING CYTOKINE PRODUCTION

PROBLEM: This study was aimed at investigating the involvement of an a ltered cytokine pattern in the immunomodulatory and anti-abortive effe cts of a progesterone-induced immunomodulatory protein (PIBF). METHOD: PIBF expression on lymphocytes of healthy pregnant women and from wom en at risk for premature pregnancy termination was determined. In sera of the same women TNF alpha was quantified by a bioassay using L929 c ells. NK activity was determined by a single cell cytotoxicity assay. Cytokine production of the lymphocytes or murine spleen cells was meas ured by ELISA or detected by immunocytochemistry. In pregnant mice end ogenous PIBF activity was neutralized by anti-PIBF IgG. RESULTS: Sera of women at risk for premature pregnancy termination contained signifi cantly higher concentrations of TNF alpha than those from healthy preg nant women and PIBF expression on the lymphocytes was inversely relate d to serum concentration of TNF alpha. Increased NK activity of lympho cytes after neutralization of endogenous PIBF activity is corrected by anti-IL2 treatment acid PIBF inhibits IL12 expression on activated ly mphocytes. PIBF increases IL-10 production by activated spleen cells. In pregnant mice, neutralization of endogenous PIBF activity by specif ic antibody results in increased resorption rate and reduced splenic I L-10 production. CONCLUSIONS: Our data allow the assumption that via b locking IL-12 production PIBF inhibits NK activation with a concomitan t reduction of TNF alpha levels. Disturbances in this system might lea d to the expression of the known synergistic effect of IL-12 and TNF a lpha, resulting in a Th1 type cytokine dominance and pregnancy termina tion.