Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.
Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.
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DOI：
10.1084/jem.164.4.1093
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发表时间：
1986-10-01
期刊：
影响因子：
--
通讯作者：
Gutterman JU
中科院分区：
文献类型：
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作者：
Kurzrock R;Rohde MF;Quesada JR;Gianturco SH;Bradley WA;Sherwin SA;Gutterman JU
患有恶性肿瘤或慢性感染的动物会出现特征性的代谢异常，包括明确的高甘油三酯血症状态。这些异常归因于活化的巨噬细胞释放一种或多种介质。我们报道，癌症患者接受了一种强效巨噬细胞激活剂rifn - γ，剂量大于或等于0.25 mg/m2/d i.m.，显示甘油三酯显著升高，但胆固醇水平没有升高（预处理甘油三酯水平为180 +/- 190 mg/dl[平均+/- SD]，而第14天的水平为370 +/- 242 mg/dl， n = 23，配对t检验p < 0.001）。这种高甘油三酯血症的特征是极低密度脂蛋白的增加和血浆肝素后脂肪酶活性的降低，与甘油三酯清除缺陷一致（预处理脂肪酶平均水平为2.1 mumol/ml/h，而一天- 14的水平为1.2 mumol/ml/h，配对t检验n = 6, p = 0.02）。在体外实验中，rIFN- γ不直接抑制脂蛋白脂肪酶的活性。其他可能的作用机制，如活化巨噬细胞释放的rifn - γ诱导介质抑制脂肪酶，或干扰素对脂肪酶生物合成的直接影响，需要进一步研究。我们的观察结果提供了免疫系统产生的因子可以调节人体脂质代谢的证据。
Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post- heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day- 14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN- gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man.