The prostaglandin E1 analogue, misoprostol, regulates inflammatory cytokines and immune functions in vitro like the natural prostaglandins E1, E2 and E3.
We examined whether some immune functions related to the action and production of cytokines could be regulated by the natural prostaglandins E (PGE) and the PGE1 (ester) analogue, Misoprostol. PGE1,2,3 and Misoprostol inhibited: (1) the mitogenic activity of interleukin-1 (IL-1) for mouse thymocytes; (2) spreading of mouse macrophages on glass; (3) tumour necrosis factor (TNF) (alpha and beta) production by human peripheral blood mononuclear cells and rat macrophages; (4) IL-1 production by rat and mouse peritoneal macrophages; and (5) interferon-gamma (IFN-gamma) production by human peripheral blood mononuclear cells. These PGE had little effect on IL-1 production by human monocytes. By contrast, they all enhanced IL-6 production by rat and mouse macrophages and human monocytes. These effects were noted at concentrations below 500 nM (even as low as 10 nM). The relative potency of the prostanoids tested for both inhibitory and stimulatory effects was PGE1 = PGE2 = or greater than PGE3 greater than Misoprostol greater than PGA2 much greater than PGF1-alpha = PGF2-alpha = PGD2 (no effect). There is strong evidence that PGE1,2,3 and Misoprostol bind to the same receptor(s) and trigger the second messenger, cAMP, since dibutyryl cAMP (a lipophilic analogue of cAMP) had the same effects as the PGE. These PGE also induced elevated intracellular cAMP levels in and competed with [3H]PGE2 for binding to human and rat cells with the same relative potencies as described above.
Haynes
D R
DR
Department of Pathology, University of Adelaide, South Australia.
Whitehouse
M W
MW
Vernon-Roberts
B
B
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D016595:Misoprostol / Q000276:immunology*; D011458:Prostaglandins E / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D016207:Cytokines; D007376:Interleukin-2; D011458:Prostaglandins E; D016595:Misoprostol; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine