Interleukin 1 and/or tumor necrosis factor-α synergize with granulocyte-macrophage colony-stimulating factor to enhance histamine synthesis in hematopoietic cells: role of prostaglandin e2

Abstract

Previouslyr1,y-stimulating factor (GM-CSF) stimulates histamine synthesis by normal murine hematopoietic cells. Addition of either interleukin (IL) 1 (α or β) or murine recombinant tumor necrosis factor (TNF)-α 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-α are mediated by prostaglandin E₂ (PGE₂) production since (a) GM-CSF together with either IL 1 or TNF-α 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-α 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-α or PGE₂, suggesting two distinct mechanisms for the induction of this biological activity in hematopoietic progenitor cells.