SOLUBLE INTERLEUKIN-6 (IL-6) RECEPTOR IN THE SERA OF PREGNANT-WOMEN FORMS A COMPLEX WITH IL-6 AND AUGMENTS HUMAN CHORIONIC-GONADOTROPIN PRODUCTION BY NORMAL HUMAN TROPHOBLASTS THROUGH BINDING TO THE IL-6 SIGNAL TRANSDUCER

To study the role of soluble interleukin-6 receptor (sIL-GR) during pr egnancy, sIL-GR levels in the sera of pregnant women in the first, sec ond, and third trimesters were determined and found to remain unchange d during pregnancy, but were significantly higher than those in nonpre gnant women in the follicular, ovulatory, and luteal phases of the men strual cycle (P < 0.001). IL-6 levels, however, in the sera of pregnan t women at all trimesters showed no difference from those in nonpregna nt women at any stage of the menstrual cycle. Recombinant sIL-6R (rsIL -6R) augmented hCG production by rIL-6-stimulated trophoblasts dose de pendently, but failed to enhance hCG production by unstimulated tropho blasts. rIL-6- and rsIL-GR-induced hCG production was significantly bl ocked by anti-IL-GR antibody, PM1; antisignal transducing glycoprotein 130 (gp130) antibody, GPX7; or a tyrosine kinase inhibitor, genistein . Thus, sIL-6R in serum from pregnant women forms a complex with place ntal and decidual IL-6 in a manner similar to trophoblast membrane-bou nd IL-6R. These two discrete types of IL-6R and IL-6 complex might act cooperatively by binding to gp130 and subsequently evoking tyrosine k inase activity in the trophoblasts to produce hCG in vivo.