Endocrine regulation of the immune system during pregnancy

Among the potentially immunosuppressive substances present in pregnancy serum, progesterone seems to play a major role in reducing in vitro responsiveness of maternal lymphocytes. Although the physiological importance of systemic immunosuppression is not clear, it seems likely that the action of progesterone is not restricted to the fetomaternal interface, where high local concentrations of this hormone are present. Sensitivity of maternal lymphocytes obtained from peripheral blood, to blocking by progesterone is increased. Relatively low concentrations of the hormone, e.g., that present in the serum are sufficient to cause depression of lymphocyte functions. Because of the diverse in vitro effects of this hormone, nearly all stages of the immune response are affected. Suppressor cells appear to play an important role in mediating this effect. Concerning the mode of action of progesterone, recent data suggest a receptor-mediated effect, in which arachidonic acid metabolism is involved. The biological significance of the above mentioned phenomena is not yet established. For elucidating this point, further experimental evidence would be needed for, or against the crucial role of progesterone-mediated immunosuppression in the maintenance of pregnancy. It is going to be difficult to dissect immunologic and other effects of progesterone in vivo, nevertheless, it seems clear that these investigations require in vivo systems. An attractive approach would be isolation and characterization of progesterone binding structures in immunocompetent cells of healthy pregnant women, and raising antibodies, which could discriminate between these binding sites and progesterone receptors of the placenta. The use of these antibodies, or receptor blockers of high specificity might provide a possibility to discriminate between immunological and other biological effects of progesterone in vivo.