Groeneveld P H, Kwappenberg K M, Langermans J A, Nibbering P H, Curtis L
Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
Cytokine. 1997 Feb;9(2):138-42. doi: 10.1006/cyto.1996.0147.
The aim of the present study was to investigate the relationship between the levels of pro-inflammatory [interleukin 6 (IL-6), IL-8, tumour necrosis factor alpha (TNF-alpha)], anti-inflammatory cytokines [IL-10, soluble TNF receptor type I (TNFsrI), TNFsrII], and the production of nitric oxide (NO) during a 1-week period in 23 patients with severe sepsis. The highest levels of pro-inflammatory cytokines and nitrate, the stable metabolite of NO, were found during the first day after inclusion and gradually declined thereafter. Detectable levels of IL-10, TNFsrI and TNFsrII were present in all patients at study entry but did not significantly change during the study period [analysis of variance (MANOVA); P > 0.05]. Serum nitrate levels correlated significantly with both pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) as well as anti-inflammatory cytokines (IL-10, TNFsrI, TNFsrII). Serum nitrate levels over time were higher in patients with positive blood cultures (n = 4) (MANOVA; P < 0.005), as compared to patients without proven bacteraemia. These data support the concept of an acute phase of sepsis that is characterized by an excess of pro-inflammatory cytokines, while anti-inflammatory cytokines are predominantly present during the secondary phase. The present findings indicate that pro-inflammatory cytokines are related to the induction of excessive NO production during the first phase of sepsis and that reduction of NO production occurs during the secondary phase. This may suggest that anti-inflammatory cytokines are able to diminish the production of NO in patients with severe sepsis.
本研究的目的是调查23例严重脓毒症患者在1周内促炎细胞因子[白细胞介素6（IL-6）、IL-8、肿瘤坏死因子α（TNF-α）]、抗炎细胞因子[IL-10、可溶性I型TNF受体（TNFsrI）、TNFsrII]水平与一氧化氮（NO）产生之间的关系。促炎细胞因子和NO的稳定代谢产物硝酸盐的最高水平在纳入后的第一天被发现，此后逐渐下降。在研究开始时，所有患者均检测到可检测水平的IL-10、TNFsrI和TNFsrII，但在研究期间没有显著变化[多变量方差分析（MANOVA）；P>0.05]。血清硝酸盐水平与促炎细胞因子（IL-6、IL-8、TNF-α）以及抗炎细胞因子（IL-10、TNFsrI、TNFsrII）均显著相关。与没有证实菌血症的患者相比，血培养阳性的患者（n = 4）随时间的血清硝酸盐水平更高（MANOVA；P < 0.005）。这些数据支持脓毒症急性期的概念，其特征是促炎细胞因子过量，而抗炎细胞因子主要在二期出现。目前的研究结果表明，促炎细胞因子与脓毒症第一阶段过量NO产生的诱导有关，而在第二阶段NO产生减少。这可能表明抗炎细胞因子能够减少严重脓毒症患者的NO产生。
