Flunoprost

Prostaglandins and Prostaglandin-analogues were investigated for their ability to protect mice from platelet-activating factor (PAF) induced shock. 75% mortality in female NMRI mice was induced by i.v. injection of 75 micrograms/kg PAF. Nileprost and PGE1, the most potent substances, produced a dose dependent protection against PAF. Iloprost and PGI2 were less effective. PGE2, nalador, flunoprost and U 46619 were neither protective nor deleterious. The strong difference in the effectiveness between the two prostaglandins of the E-series and the poor effect of PGI2 and the PGI2 analogue is remarkable. Flunoprost and U 46619 that increased the TXB2 synthesis or release in two experimental models did not enhance the PAF mortality; TXA2 seems to be only a secondary mediator of the acute PAF-induced death.

Treatment of mice bearing allogeneic tail skin grafts with iloprost, a stabilized prostacyclin derivative, as well as dexamethasone prolonged graft survival. Nalador and flunoprost, stabilized prostaglandin E analogues, had similar but weaker effects. The thromboxane agonist U 46619 had no effect on graft rejection. An incubation of human monocytes with iloprost or prostaglandin E2 led to a dose-dependent reduction of HLA-DR antigen expression by these cells. Furthermore, a suppressive effect of these prostaglandin derivatives on the calcium ionophore stimulated release of arachidonic acid metabolites by human polymorphonuclear leukocytes has been shown, which demonstrates an antiinflammatory action of these drugs. Additionally, the eicosanoids were determined in the tail skin after complete allograft rejection. The importance of thromboxane for the rejection of skin grafts has not been confirmed. These data, along with the known antiaggregatory and antiischemic cytoprotective effects of iloprost, suggest that this newly developed drug may be all the more important in clinical organ transplantation.