Interleukin 1 and/or tumor necrosis factor-alpha synergize with granulocyte-macrophage colony-stimulating factor to enhance histamine synthesis in hematopoietic cells: role of prostaglandin E2.

Previously, we have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates histamine synthesis by normal murine hematopoietic cells. Addition of either interleukin (IL) 1 (alpha or beta) or murine recombinant tumor necrosis factor (TNF)-alpha to murine recombinant GM-CSF (at optimal or suboptimal concentrations) enhances its activity on bone marrow histamine synthesis up to 70%. Evidence is provided that these synergies between GM-CSF and IL 1 or TNF-alpha are mediated by prostaglandin E2 (PGE2) production since (a) GM-CSF together with either IL 1 or TNF-alpha stimulates PGE2 synthesis by bone marrow cells, while none of these factors does it alone; (b) exogenous PGE2 (ranging from 10(-6) M to 10(-10) M) potentiates GM-CSF-induced histamine synthesis in a dose-dependent manner; and (c) indomethacin, a cyclooxygenase inhibitor, completely abrogates the synergistic action of IL 1 and TNF-alpha on GM-CSF-induced histamine generation. Conversely, histamine synthesis promoted by IL 3, the unique cytokine sharing this property with GM-CSF, cannot be modulated by IL 1, TNF-alpha or PGE2, suggesting two distinct mechanisms for the induction of this biological activity in hematopoietic progenitor cells.