Tschoeke Sven K, Oberholzer Andreas, Moldawer Lyle L
Department of Trauma and Reconstructive Surgery, Charité--University Hospitals Berlin, Campus Benjamin Franklin, Germany.
Crit Care Med. 2006 Apr;34(4):1225-33. doi: 10.1097/01.CCM.0000208356.05575.16.
Severe inflammation and sepsis remain a serious clinical challenge worldwide. Despite modern supportive medicine and an improved understanding of the underlying pathophysiology, mortality rates remain high in patients suffering from this severe inflammatory process. The often excess production of pro- and anti-inflammatory cytokines frequently found in the circulation of septic patients has stimulated the search for reliable inflammatory mediators that can be used for the diagnosis and prediction of clinical outcome. Interleukin (IL)-18, formerly termed interferon-gamma inducing factor, is a pro-inflammatory and Th1 cytokine suggested to play a significant role in the pathogenesis of this disease. This review focuses on our current understanding of the pro-inflammatory cytokine, IL-18, and its potentially unique role in sepsis.
Bibliographic search of the most recent literature (1995-2005) relating to IL-18 and its role in inflammatory diseases, with emphasis on its pathophysiological importance in sepsis. In addition, a summary of the author's own experimental data from this particular field of research set in the context of current knowledge regarding IL-18.
Several studies have shown elevated plasma IL-18 concentrations to be associated with poor clinical outcome in severe inflammatory and septic conditions. Moreover, a significant increase in IL-18 concentrations has been shown to discriminate between Gram-positive and Gram-negative related sepsis, and, thus, may potentially augment existing diagnostic tools. Biological neutralization of IL-18 via caspase-1 intervention or through the administration of IL-18-binding protein has been promulgated as a promising therapeutic approach, but additional studies are required to evaluate its full potential in acute inflammatory diseases.
严重炎症和脓毒症仍是全球范围内严峻的临床挑战。尽管现代支持性医学不断发展，且对潜在病理生理学的认识有所提高，但患有这种严重炎症过程的患者死亡率仍然很高。脓毒症患者循环中经常出现的促炎和抗炎细胞因子往往过度产生，这促使人们寻找可用于诊断和预测临床结局的可靠炎症介质。白细胞介素（IL）-18，以前称为干扰素-γ诱导因子，是一种促炎和Th1细胞因子，被认为在这种疾病的发病机制中起重要作用。本综述重点关注我们目前对促炎细胞因子IL-18及其在脓毒症中潜在独特作用的理解。
对1995年至2005年期间与IL-18及其在炎症性疾病中的作用相关的最新文献进行文献检索，重点关注其在脓毒症中的病理生理重要性。此外，结合当前关于IL-18的知识，总结作者在该特定研究领域的自身实验数据。
多项研究表明，在严重炎症和脓毒症情况下，血浆IL-18浓度升高与不良临床结局相关。此外，已表明IL-18浓度的显著增加可区分革兰氏阳性和革兰氏阴性相关脓毒症，因此可能会增强现有的诊断工具。通过半胱天冬酶-1干预或给予IL-18结合蛋白对IL-18进行生物中和已被宣传为一种有前景的治疗方法，但还需要更多研究来评估其在急性炎症性疾病中的全部潜力。
