The immunosuppressive potential of misoprostol--efficacy and variability

Existing evidence on the immunosuppressive efficacy of prostaglandin E (PGE) and its analogues in vivo is conflicting. We investigated the effect of misoprostol, an orally available PGE1 analogue, on T-cell proliferation, Th cell-derived cytokine production, and phagocytosis in healthy volunteers. All participants (n=20) received increasing doses of misoprostol (0-400 microg). Blood was drawn before and after intake. Misoprostol intake caused a time- and dose-dependent reduction of anti-CD3-stimulated cell proliferation. Whereas the synthesis of Th1 cytokines (IL-2 and IFN-gamma) was dose-dependently reduced, IL-10 expression was increased at lower misoprostol doses. Concerning IL-4 expression, we observed an increased IL-4 production in males, but a decreased IL-4 production in females. Misoprostol intake also reduced phagocytosis activity in a dose-dependent manner. At least in part our results explain the immunosuppressive effects of misoprostol observed in vivo. The considerable interindividual variability as well as gender-specific differences seem to account for the variability of clinical study results.