Tilg H, Vogel W, Wiedermann C J, Shapiro L, Herold M, Judmaier G, Dinarello C A
Department of Medicine, New England Medical Center Hospitals, Boston, Massachusetts 02111.
Hepatology. 1993 Nov;18(5):1132-8.
The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.
促炎细胞因子白细胞介素-1和肿瘤坏死因子-α被认为在肝病的病理生理学中起重要作用。近年来已发现这些细胞因子的特异性拮抗剂。白细胞介素-1受体拮抗剂是一种特异性白细胞介素-1拮抗剂。源自细胞表面p55肿瘤坏死因子受体p55的可溶性受体是一种天然存在的物质，可抑制肿瘤坏死因子的生物学效应。我们使用特异性放射免疫分析法检测了14例急性病毒性肝炎患者和160例各种慢性肝病患者循环中的白细胞介素-1受体拮抗剂和肿瘤坏死因子可溶性受体p55水平。无论病因如何，大多数慢性肝病患者以及病毒性肝炎患者的白细胞介素-1受体拮抗剂水平，尤其是肿瘤坏死因子可溶性受体水平均显著升高。慢性肝病和肝硬化患者的两种细胞因子拮抗剂水平均显著高于非肝硬化患者。白细胞介素-1受体拮抗剂与肿瘤坏死因子可溶性受体之间的相关性比任何一种拮抗剂与C反应蛋白或血沉之间的相关性都更显著。白细胞介素-1受体拮抗剂和肿瘤坏死因子可溶性受体水平也与胆红素和谷草转氨酶水平呈正相关。我们得出结论，白细胞介素-1受体拮抗剂和肿瘤坏死因子可溶性受体的循环水平可能反映了疾病的持续活动，并可能调节内源性白细胞介素-1和肿瘤坏死因子的某些作用。
