Bertini R, Bianchi M, Villa P, Ghezzi P
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Int J Immunopharmacol. 1988;10(5):525-30. doi: 10.1016/0192-0561(88)90069-0.
Different recombinant cytokines were studied for their effects on mouse liver in vivo: interleukin 1-alpha and -beta, tumor necrosis factor, lymphotoxin, interferon-alpha A/D and gamma depressed liver cytochrome P450-dependent drug metabolism (measured by ethoxycoumarin deethylase activity) 24 h after treatment, at doses in the microgram range, while IL-2 had no effect on this enzymatic system. Interleukin 1 (both alpha and beta), tumor necrosis factor and lymphotoxin also increased plasma fibrinogen, a marker of liver acute phase inflammatory response. Interferon-gamma and tumor necrosis factor had an additive effect in depressing liver drug metabolism. When tested in vitro on isolated hepatocytes, only interleukin 1 depressed P450-dependent drug metabolism, while all the other cytokines were inactive, thus suggesting that their effect on the liver in vivo is not a direct effect but is mediated by other mediators.
白细胞介素1-α和-β、肿瘤坏死因子、淋巴毒素、干扰素-α A/D和γ在微克级剂量处理24小时后会抑制肝脏细胞色素P450依赖性药物代谢（通过乙氧香豆素脱乙基酶活性测定），而IL-2对该酶系统无影响。白细胞介素1（α和β）、肿瘤坏死因子和淋巴毒素也会增加血浆纤维蛋白原，这是肝脏急性期炎症反应的一个指标。干扰素-γ和肿瘤坏死因子在抑制肝脏药物代谢方面具有相加作用。在体外对分离的肝细胞进行测试时，只有白细胞介素1会抑制P450依赖性药物代谢，而所有其他细胞因子均无活性，因此表明它们在体内对肝脏的作用不是直接作用，而是由其他介质介导的。
