Production of interleukin-1α, interleukin-1β and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor

Recent studies have examined the synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and hematopoietin-1 (now identified as Interleukin-1, IL-1) on bone marrow colony formation. In the present report, human peripheral blood mononuclear cells (MNCs) were stimulated in vitro with recombinant human GM-CSF (rGM-CSF) and production of IL-1α, IL-1β, and tumor necrosis factor (TNF) was measured by specific radioimmunoassays. In the MNCs of 20 individuals, rGM-CSF's ability to induce the three cytokines was variable. Nearly all donors responded to low-dose rGM-CSF (0.02 to 2 ng/mL) with production of TNF, whereas some individuals did not produce IL-1α or IL-1β. The MNCs from some subjects stimulated with high-dose rGM-CSF (10 to 80 gn/mL) produced as much cytokine as in response to 100 ng/mL endotoxin. Localization (ie, extracellular or cell-associated cytokine) was specific for the cytokine rather than the stimulus. Indomethacin increased the amount of cytokine produced in response to rGM-CSF for IL-1β and TNF but not for IL-1α. In addition, interferon-γ (INF-γ) upregulated the amount of TNF induced by rGM-CSF in all donors examined, with variable effect on IL-1α and IL-1β. Suboptimal levels of endotoxin incubated with rGM-CSF did not alter the amount of IL-1 produced as compared with cells stimulated with rGM-CSF alone, whereas TNF production showed either no change or a slight decrease in production. These data suggest that GM-CSF may play an important role in the host defense response by stimulating production of these cytokines.