PRODUCTION OF INTERLEUKIN-1-ALPHA, INTERLEUKIN-1-BETA AND TUMOR NECROSIS FACTOR BY HUMAN MONONUCLEAR-CELLS STIMULATED WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Google Scholar
  • 1 October 1988
    • journal article
    • research article
    • Vol. 72  (4) , 1368-1374
Abstract
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-1.alpha., IL-1.beta., 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 prodution of TNF, whereas some individuals did not produce IL-1.alpha. or IL-1.beta.. The MNCs from some subjects stimulated with high-dose rGM-CSF (10 to 80 ng/mL) produced as much cytokine as in response to 10 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-1.beta. and TNF but not for IL-1.alpha.. In addition, interferon-.gamma. (IFN-.gamma.) upregulated the amount of TNF induced by rGM-CSF in all donors examined, with variable effect on IL-1.alpha. and IL-1.beta.. 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 changes 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.

This publication has 31 references indexed in Scilit: