Radioprotective effects of combination broncho-vaxom, a macrophage activator, and indomethacin, an inhibitor of prostaglandin production: relationship to myelopoiesis.

Abstract

The effects of the bacterial extract broncho-vaxom (BV; radioprotective immunomodulator; 500 micrograms/mouse i.p., -24 h) and indomethacin (INDO; inhibitor of prostaglandin production; 2 x 40 micrograms/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 in all treatment groups, with combination-treated mice exhibiting the greatest effects. Similarly, 24 h after combined administration of BV and INDO (i.e. at the time of presumed irradiation) to the non-irradiated mice granulocyte-macrophage colony-forming cell (GM-CFC) numbers were greater in the bone marrow and spleen. Also, as determined by hydroxyurea 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 significant proliferation as compared to GM-CFC in the spleen of mice injected with BV alone. Combined modality treatment was also more effective than single agent treatments in accelerating bone marrow cellularity and GM-CFC regeneration, but not in accelerating GM-CFC regeneration in the spleen. Combined administration of BV and INDO to mice prior to lethal irradiation exerted an additional radioprotective effect and protected 95% of the C57Bl/6 mice.