Dofferhoff A S, de Jong H J, Bom V J, van der Meer J, Limburg P C, de Vries-Hospers H G, Marrink J, Mulder P O, Weits J
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Scand J Infect Dis. 1992;24(2):197-204. doi: 10.3109/00365549209052612.
Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.
脓毒症或脓毒性休克常与补体系统激活、凝血和纤溶改变以及多种细胞因子释放相关。在本研究中，我们分析了20例临床诊断为脓毒症的连续患者中补体激活与炎症介质、血流动力学和生化参数以及疾病严重程度和预后的关系。与7例非脓毒性休克患者中分别为14%和42%的比例相比，90%的患者C3a和C3d水平升高（中位数水平分别为0.19mg/l和8.6mg/l）。20例脓毒症患者中仅有1例C4水平降低。94%和100%的患者TNF和IL-6水平升高，TNF和IL-6水平分别升高（中位数水平为122ng/l和1300U/ml），且明显相关（r = 0.67，p小于0.01）。C3a水平与APACHE II评分相关（r = 0.57，p小于0.05），高C3a水平与致命结局相关（p小于0.05）。C3a也与平均动脉压呈负相关（r = 0.50，p小于0.01）。补体C3a和C3d水平与纤溶酶原激活物抑制剂-1（PAI）水平显著相关，与抗凝血酶III（AT-III）水平呈负相关。我们发现这些补体产物与白细胞计数或乳酸水平之间无相关性，C3a或C3d与细胞因子TNF和IL-6之间也无相关性。与所有患者IL-6水平明显下降以及存活患者TNF水平下降相反，C3a和C3d水平在治疗的最初24小时内未显著下降。非存活患者的TNF水平保持稳定或升高。我们得出结论，补体系统和细胞因子系统均参与脓毒性休克的发病机制，可能参与低血压和弥散性血管内凝血等一些致命并发症的发生发展。
