Effect of macrophage colony-stimulating factor (M-CSF) on mouse immune responses in vivo.

We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500 mu g/ml) increased Mac-1(+) cell numbers in the peritoneal cavity. The tumoricidal activities of the macrophages from vehicle-administered (V-M Phi) and from rhM-CSF-administered (M-M Phi) mice were the same as those observed in vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal activity of M-M Phi was stronger than that of V-M Phi. Intravenous administration of rhM-CSF (500 mu g/gk) increased the number of spleen cells. Flow cytometric analysis showed that administration of rhM-CSF increased Mac-1(+), B220(+) and NK 1.1(+) cell counts in the spleen. However, CD4(+) and CD8(+) cell numbers did not change. Concomitant increases were observed in levels of IL-4 and IL-10 in mouse serum following rhM-CSF administration, but no significant changes were observed in the serum level of IFN-gamma. In experiments involving mouse immune responses, the administration of rhM-CSF reduced the contact sensitivity (CS) reaction against picryl chloride (PC) and augmented IgE production in response to 2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgG1. These results suggest that administration of rhM-CSE not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.