THE IMMUNOSUPPRESSIVE PROPERTIES OF NEW ORAL PROSTAGLANDIN-E1 ANALOGS

Prostaglandins play an important role in cell-me-diated immune responses. Their clinical use has been limited by poor oral bioavailability, short half-lives, and significant toxicity profiles. We studied the immunosuppressive properties of new, synthetic, prostaglandin Ex (PGE1) methyl ester analogs (misoprostol, enisoprost) with oral bioavailability using an allogeneic in vitro immunoassay. Our results show that the PGE1analogs suppress alloproliferative responses and supplement the immunosuppressive activity of cyclosporine and methylprednisolone. Moreover, we demonstrate that addition of recombinant interleukin-2 to the PGE1analogs restores alloimmune responsiveness and the expression of surface class II antigen and IL-2 receptors on responder lymphocytes. These studies, together with preliminary in vivo data in rodents and man, suggest that the new synthetic oral PGE1analogs may provide therapeutic efficacy in clinical transplantation and a variety of immunologically mediated diseases. © 1990 by Williams & Wilkins.