Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.
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.
D000328:Adult; D000368:Aged; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D011994:Recombinant Proteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008071:Lipoprotein Lipase