Studies on polymorphonuclear leukocyte bactericidal function: the role of exogenous cytokines.

Abstract

We investigated the effects of exogenous cytokines (interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and IL-1 beta) on polymorphonuclear neutrophil (PMN) bactericidal activity against both Staphylococcus aureus and Escherichia coli. Both baseline and IL-8-stimulated PMN bactericidal activity against E. coli, but not against S. aureus, declined significantly from 0 to 240 min. The decline in bactericidal activity was prevented by TNF-alpha, but not IL-1 beta. Bactericidal activity against both E. coli and S. aureus declined as PMN:target ratios went from 20:1 to 5:1. TNF-alpha and IL-1 beta preserved bactericidal activity even at a 5:1 PMN:target ratio against E. coli, whereas all three cytokines preserved bactericidal activity at a 5:1 PMN:target ratio against S. aureus. Dose-response curves demonstrated significant increases in bactericidal activity with physiologically relevant concentrations of cytokines (IL-8: .1-10 ng/mL; TNF-alpha: 1-10(2) U/mL; and IL-1 beta: 0-10 ng/mL). Binding of cytokine receptors with monoclonal antibodies directed against IL-8R Type A, TNF-alpha R (p60) or (p80), and IL-1 beta R Type I significantly reduced the effect of individual cytokines on PMN bactericidal activity. Inhibition of terminal, but not proximal, products of the PMN oxidative burst significantly reduced the effect of exogenous cytokines on PMN bactericidal activity. These results demonstrate that individual cytokines at relatively low concentrations enhance PMN bactericidal activity via oxidant-dependent mechanisms and that inhibiting cytokine functions may not be advantageous at infectious foci in vivo.