Macrophage colony-stimulating factor induces interleukin-8 production in human monocytes

We have investigated the stimulatory effect of recombinant human macrophage colony-stimulating factor (rhM-CSF) on interleukin-8 (IL-8) production by human peripheral blood monocytes. When monocytes were prepared from peripheral blood and cultured for 24 hours, the average amount of IL-8 in the culture medium was about 8.9 +/- 3.2 ng/2 x 10(5) cells. In contrast, the production of IL-8 by monocytes increased to a level of 19.2 +/- 4.7 ng/2 x 10(5) cells in response to rhM-CSF. This induction by rhM-CSF was dose-dependent. Northern blot analysis showed that expression of IL-8 at the pretranslational level was enhanced after M-CSF treatment. Kinetic studies showed that secretion of IL-8 from monocytes was enhanced within 2 hours after exposure to rhM-CSF, and a saturation level, which was reached around 48 hours, was two-fold higher than that of cells without M-CSF treatment. In addition, conditioned medium of M-CSF-stimulated monocytes activated the chemotaxis of human neutrophils, and this activity was significantly inhibited by anti-IL-8 antibody. These results, taken together, suggest that M-CSF can affect many cellular functions through regulation of IL-8 expression in monocytes.