Simms H H, D'Amico R
Brown University School of Medicine, Division of Surgical Research, Rhode Island Hospital, Providence 02903, USA.
Shock. 1997 Feb;7(2):84-9. doi: 10.1097/00024382-199702000-00002.
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.
我们研究了外源性细胞因子（白细胞介素（IL）-8、肿瘤坏死因子（TNF）-α和IL-1β）对多形核中性粒细胞（PMN）针对金黄色葡萄球菌和大肠杆菌的杀菌活性的影响。从0到240分钟，针对大肠杆菌而非金黄色葡萄球菌的基线和IL-8刺激的PMN杀菌活性均显著下降。TNF-α可防止杀菌活性下降，但IL-1β不能。随着PMN与靶标的比例从20:1降至5:1，针对大肠杆菌和金黄色葡萄球菌的杀菌活性均下降。即使在PMN与靶标比例为5:1时，TNF-α和IL-1β仍能保持针对大肠杆菌的杀菌活性，而所有三种细胞因子在PMN与靶标比例为5:1时均能保持针对金黄色葡萄球菌的杀菌活性。剂量反应曲线表明，在生理相关浓度的细胞因子（IL-8：0.1 - 10 ng/mL；TNF-α：1 - 10² U/mL；IL-1β：0 - 10 ng/mL）作用下，杀菌活性显著增加。用针对IL-8R A型、TNF-α R（p60）或（p80）以及IL-1β R I型的单克隆抗体结合细胞因子受体，可显著降低单个细胞因子对PMN杀菌活性的影响。抑制PMN氧化爆发的终末产物而非近端产物，可显著降低外源性细胞因子对PMN杀菌活性的影响。这些结果表明，相对低浓度的单个细胞因子通过依赖氧化剂的机制增强PMN杀菌活性，并且在体内感染灶抑制细胞因子功能可能并无益处。
