Citation

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