RADIOPROTECTIVE EFFECTS OF COMBINATION BRONCHO-VAXOM, A MACROPHAGE ACTIVATOR, AND INDOMETHACIN, AN INHIBITOR OF PROSTAGLANDIN PRODUCTION - RELATIONSHIP TO MYELOPOIESIS

The effects of the bacterial extract broncho-vaxom (BV; radioprotectiv e immunomodulator; 500 mu g/mouse i.p., - 24 h) and indomethacin (INDO ; inhibitor of prostaglandin production; 2 x 40 mu g/mouse i.m., - 24 h and - 3 h) on the post-irradiation recovery of hemopoietic functions in mice were investigated. Both agents were administered either alone or in combination. Endogenous spleen colony formation was increased i n all treatment groups, with combination-treated mice exhibiting the g reatest effects. Similarly, 24 h after combined administration of BV a nd INDO (i.e. at the time of presumed irradiation) to the non-irradiat ed mice granulocyte-macrophage colony-forming cell (GM-CFC) numbers we re greater in the bone marrow and spleen. Also, as determined by hydro xyurea injection, there was an increase in the number of GM-CFC in the S-phase of the cell cycle in the bone marrow. However, GM-CFC in the spleen of combination pretreated mice was not stimulated to significan t proliferation as compared to GM-CFC in the spleen of mice injected w ith BV alone. Combined modality treatment was also more effective than single agent treatments in accelerating bone marrow cellularity and G M-CFC regeneration, but not in accelerating GM-CFC regeneration in the spleen. Combined administration of BV and INDO to mice prior to letha l irradiation exerted an additional radioprotective effect and protect ed 95% of the C57B1/6 mice.