Activation of human polymorphonuclear neutrophil functions by interferon-γ and tumor necrosis factors

Recombinant human interferon-γ (rHuIFN-γ) and natural human tumor necrosis factor β (nHuTNF-β) (previously called lymphotoxin), purified to homogeneity, were used to assess their effects on certain functions of human polymorphonuclear neutrophils (PMN) in vitro. The treatment of PMN with 100 U of either rHuIFN-γ or nHuTNF-β for 20 min significantly increased their ability to phagocytize 1.5 μm latex beads as detected by flow cytometry. Preparations of recombinant human TNF-β (rHuTNF-β) showed activities similar to those of its natural counterpart in activating phagocytosis. In addition, a significant enhancement in PMN-medicated antibody-dependent cellular cytotoxicity was observed after treatment for 2 hr with IFNγ and both TNF-α and TNF-β. The enhancement by treatment with a combination of rHuIFN-γ and nHuTNF-β exceeded the enhancement caused by either agent alone. We also show that although lipopolysaccharide (LPS) is a potent stimulator of PMN function, polymyxin B can block PLS-induced but not lymphokine-induced activation. These data demonstrate new activities for both TNF-α and TNF-β in augmenting the phagocytic and cytotoxic activities of PMN.