Gender difference in tumor necrosis factor-α production in human neutrophils stimulated by lipopolysaccharide and interferon-γ

The gender difference in tumor necrosis factor-alpha (TNF-alpha) production in human neutrophils stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was explored by using peripheral blood neutrophils from young men and women. As compared with female neutrophils, male neutrophils released greater amounts of TNF-alpha, and exhibited stronger activation of mitogen-activated protein kinases and phosphatidylinositol 3-kinase in response to LPS stimulation. LPS-induced TNF-alpha production was markedly enhanced by pretreatment of cells with IFN-gamma, and IFN-gamma-mediated priming in male neutrophils was significantly greater than that in female neutrophils. Male neutrophils showed higher expression of TLR4, but not IFN-gamma receptors, than female neutrophils, and its expression was increased by stimulation with IFN-gamma or IFN-gamma plus LPS. These findings indicate that male neutrophils show higher responsiveness to stimulation with LPS and IFN-gamma than female neutrophils, and suggest that the gender difference in neutrophil responsiveness to LPS and IFN-gamma is partly responsible for that in the outcome of sepsis, in which premenopausal women show a favorable prognosis as compared with men. (C) 2013 Elsevier Inc. All rights reserved.