Dinarello C A
University of Colorado Health Sciences Center, Denver 80262, USA.
Eur Cytokine Netw. 2000 Sep;11(3):483-6.
Although IL-18 is an inducer of IFN-gamma and Th1 responses. IL-18 is a proinflammatory cytokine by several criteria. In several animal models. antibodies that neutralize endogenous IL-18 reduce the severity of disease. Endotoxin lethality is prevented by anti-IL-18. Even in models that are interferon-y independent, neutralization of IL-18 prolongs survival. Anti-IL-18 also protects the liver against cellular injury induced by toxins or activated T cells. In models of hepatic melanoma metastasis. IL-18 blockade reduces the adherence of malignant cells by preventing IL-18 upregulation of vascular endothelial adhesion-1 molecule expression. IL-18 and IL-12 act synergistically to stimulate I cells and natural killer cells to produce IFN-gamma but neutralization of IL-18 prevents IL-12 induction of IFN-gamma. IL-18. like several cytokines. can be used to enhance host defense against tumors in mice a mechanism that is most often IFN-gamma-dependent. Nevertheless. it is the proinflammatory portfolio of IL-18 which likely contributes to enhanced host defenses. In models or arthritis, lung injury or inflammatory bowel disease, neutralization of IL-18 reveals the important role of this cytokine in mediating inflammation.
尽管白细胞介素-18是γ干扰素和Th1反应的诱导剂，但从多个标准来看，白细胞介素-18是一种促炎细胞因子。在多种动物模型中，中和内源性白细胞介素-18的抗体可减轻疾病的严重程度。抗白细胞介素-18可预防内毒素致死。即使在不依赖干扰素-γ的模型中，中和白细胞介素-18也能延长生存期。抗白细胞介素-18还能保护肝脏免受毒素或活化T细胞诱导的细胞损伤。在肝黑色素瘤转移模型中，白细胞介素-18阻断可通过阻止白细胞介素-18上调血管内皮黏附分子-1的表达来减少恶性细胞的黏附。白细胞介素-18和白细胞介素-12协同作用刺激I细胞和自然杀伤细胞产生γ干扰素，但中和白细胞介素-18可阻止白细胞介素-12诱导γ干扰素的产生。与几种细胞因子一样，白细胞介素-18可用于增强小鼠对肿瘤的宿主防御，这一机制通常依赖γ干扰素。然而，可能正是白细胞介素-18的促炎特性有助于增强宿主防御。在关节炎、肺损伤或炎症性肠病模型中，中和白细胞介素-18揭示了这种细胞因子在介导炎症中的重要作用。
