Interleukin-10 is produced by human uterine natural killer cells but does not affect their production of interferon-gamma

A predominance of T helper (Th)2-type cytokines and a weakening of Th1 resp onses seem to be critical for the maintenance of a successful gestation. Am ong Th2-type cytokines, interleukin (IL)-10 is produced by human cytotropho blasts and defects in this production result in specific pathological condi tions of pregnancy. The current opinion is that IL-10 serves to protect the fetus from a harmful maternal immune response. However, production of the cytokine and its direct effect on uterine natural killer (uNK) cells, which represent the predominant lymphocyte population infiltrating the pregnant endometrium, are largely unknown. Thus, to shed light on the cytokine netwo rk at the maternal-fetal barrier during early pregnancy, we investigated th e IL-10 system in uNK cells. We showed that uNK cells express the mRNA tran scripts for IL-10 and IL-10 receptor. Production of IL-10 by the uNK cells was enhanced by both IL-2 and IL-12. Treatment with IL-10 alone enhanced uN K cell cytotoxic activity. In contrast, the cytokine did not modify the bas al or stimulated production of interferon (IFN)-gamma by uNK. Thus, IL-10 d oes not act as a direct antagonist of uNK cell function and activation. How ever, IL-10 produced by uNK cells in response to IL-12 and IL-2 may still h ave a feedback inhibitory effect on the production of deleterious cytokines within the uterine microenvironment.