Enhanced resistance of bone marrow transplanted mice to bacterial infection induced by recombinant granulocyte-macrophage colony- stimulating factor

Abstract

The in vivo effect of recombinant murine granulocyte-macrophage colony stimulating factor (rGM-CSF) on the resistance of mice to bacterial infection and on the number and function of neutrophils was studied in lethally irradiated mice transplanted with syngeneic bone marrow cells. Bone marrow transplanted (BMT) mice were injected intraperitoneally with 150 ng rGM-CSF or buffer solution (diluent) twice daily for 18 consecutive days. Total neutrophil recovery from the peripheral blood and the number of neutrophils mobilized into the peritoneal cavity were accelerated in rGM-CSF-treated recipients. Peritoneal neutrophils isolated from mice treated with rGM-CSF exhibited primed superoxide generation (O2-) after in vitro stimulation with suboptimal concentrations of phorbol myristate acetate (PMA), as compared with control mice (treated with diluent). No additional increase in O2- production occurred upon in vitro incubation of these cells with rGM- CSF. The protective activity of rGM-CSF was examined in mice injected with Salmonella typhimurium. There was a 44- and 9-fold increase in the number of S typhimurium at 96 hours postinfection in the spleen and liver, respectively, of control mice, as compared with rGM-CSF-treated mice, after a single injection of the bacteria (3 X 10(7) per mouse). All the untreated control mice died within 14 days postinoculation (1 X 10(7) bacteria per mouse), whereas 35% of the mice treated with rGM-CSF remained alive for more than 30 days postinfection. These findings support the concept that increased granulopoiesis and enhanced functional activity of phagocytic cells is induced by rGM-CSF and is responsible for enhanced resistance of BMT mice to bacterial infection.