COMBINED-MODALITY RADIOPROTECTION - ENHANCEMENT OF SURVIVAL AND HEMATOPOIETIC RECOVERY IN GAMMA-IRRADIATED MICE BY THE JOINT USE OF LIPOSOMAL MURAMYL TRIPEPTIDE PHOSPHATIDYLETHANOLAMINE (MTP-PE) AND INDOMETHACIN

We have reported previously [Fedorocko, P.; Int. J. Ridiat. Biol. 65:4 65, 1994] that liposomal muramyl tripeptidephosphatidyl ethanolamine ( MTP-PE/MLV) given prior to irradiation results in augmented hemopoieti c recovery and enhanced animal survival as evidenced by increased plur ipotent stem cells (CFU-S) and progenitor cells committed to granulocy te and/or macrophage development (GM-CFC) or white blood cells, neutro phil counts, as well as by survival rates of lethally irradiated mice. In this report the effects of liposomal MTP-PE (radioprotective immun omodulator; 10 mg/kg i.p., 24 h before irradiation) and indomethacin ( inhibitor of prostaglandin production; 2 mg/kg i.m., 24 h and 3 h befo re irradiation) were studied. Both of the agents were administered eit her alone or in combination. The results included the assessment of pr eirradiation hemopoietic effects of drugs and postirradiation hemopoie tic recovery in terms of bone marrow cellularity, number of bone marro w GM-CFC, endogenous spleen colony formation (endoCFU-S), and the dete rmination of the survival of lethally irradiated mice. Experimental ev idence elevated by the increased preirradiation numbers of GM-CFC and hydroxyurea kill of GM-CFC as well as a simultaneous significant dimin ution in bone marrow cellularity indicated that the beneficial action of the combined treatment could be a consequence of increased cell pro liferation in the hemopoietic tissue and mobilization with redistribut ion of stem cells from bone marrow into the circulation. In the postir radiation period (3-14 days), combined pretreatment of mice accelerate d myelopoietic regeneration in the bone marrow compared to treatment w ith MTP-PE/MLV alone or indomethacin alone. Combined administration of MTP-PE/MLV (10 mg/kg, -24 h, i.p.) and indomethacin (2 mg/kg, -24 h a nd -3 h, i.m.) to mice, prior to lethal irradiation, exerted an additi onal radioprotective effect and protected 100% of the C57B1/6 mice. Co pyright (C) 1996 International Society for Immunopharmacology