PROLONGATION OF MURINE SKIN ALLOGRAFTS BY PROSTAGLANDIN E

Abstract

The effects of 16,16-dimethyl prostaglandin E2 methyl ester (di-M-PGE2) and indomethacin (an inhibitor of endogenous prostaglandin biosynthesis) on mouse skin allograft survival were studies in B10.D2 female mice receiving skin allografts from (B10.BR X B10.D2)F1 mice. Control animals with and without i.p. diluent injections had a mean allograft survival of 13.8+/-0.6 and 13.5+/-0.5 days, respectively. Daily administration of di-M-PGE2 (200 microng/kg) prolonged mean allograft survival, both when administered alone, 16.7+/-0.6 days (P less than 0.001), or with indomethacin, 4 mg/kg thrice weekly, 16.0+/0.6 days (P less than 0.005). Increasing concentrations of indomethacin (4, 6, and 8 mg/kg thrice weekly) were inversely corrleated with allograft survival ((12.7+/-0.2, 11.8+/-0.2, and 10.9+/-0.4 days, respectively), coefficient of correlation=-0.6986; P less than 0.001. Mean plasma PGE levels at the time of total allograft rejection were 879+/-80 pg/ml in control, 717+/-59 pg/ml in 100 micron g of indomethacin-treated mice, and 654+/-59 pg/ml in 200 microng of indomethacin-treated mice (P less than 0.05). Exogenous di-M-PGE2 prolonged skin allograft survival in mice. Inhibition of endogenous prostaglandin biosynthesis by indomethacin chortened allograft survival, but this effect was completely abrogated by concurrent injection of di-M-PGE2.