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.
Waiser
Johannes
J
Department of Internal Medicine-Nephrology, University Hospital Charité, Campus Mitte, Humboldt-University, Berlin, Germany. johannes.waiser@charite.de
Böhler
Torsten
T
Stoll
Juliane
J
Schumann
Brit
B
Budde
Klemens
K
Neumayer
Hans-Hellmut
HH
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D016595:Misoprostol / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D007166:Immunosuppressive Agents; D007378:Interleukins; D016595:Misoprostol; D007371:Interferon-gamma