Hydrocortisone and inhibitors of prostaglandin synthesis. Potentiation of allograft survival in mice.
We studied the effects on survival of allogeneic skin grafts after treatment with hydrocortisone and/or inhibitors of prostaglandin synthesis: indomethacin and flufenamate. We found a marked synergistic effect of combined treatment with hydrocortisone and indomethacin or flufenamate. Neither hydrocortisone nor indomethacin or flufenamate, when given alone in relatively small doses, caused delayed graft rejection. However, when small doses of hydrocortisone were used in combination with flufenamate or indomethacin, the median survival time (MST) of allogeneic grafts was prolonged from 11.4 days to 20.9 and 23.8 days, respectively. Moreover, the increase in graft survival was comparable to that obtained by treatment with relatively high doses of azathioprine alone or combined with hydrocortisone. The finding of synergism between low doses of prostaglandin synthesis inhibitors and glucocorticoids in delaying graft rejection suggests that such treatment might provide a relatively safer means of achieving clinical immunosuppression than the high doses of steroids and azathioprine currently in use.