Interleukin-6 Causes Hypocholesterolemia in Middle-aged and Old Rhesus Monkeys

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Abstract
Background. Hypocholesterolemia is a risk factor for morbidity and mortality in older people. We have hypothesized that hypocholesterolemia in older people is due to the chronic effect of proinflammatory cytokines on lipoprotein metabolism. Methods. To test the effects of the chronic administration of interleukin-6 (IL-6) on lipoprotein levels in middle-aged and old rhesus monkeys, five middle-aged and five old rhesus monkeys received a subcutaneous injection of recombinant human IL-6 (15 μg/kg) for 28 days. Lipid, apolipoprotein, and albumin levels were measured at 0, 28, and 42 days after injection. Results. Total and HDL cholesterol levels fell by 16 and 23%, respectively, after IL-6 injections. The concentrations of apolipoproteins A I and B also decreased. The changes in lipoprotein levels were accompanied by a decrease in albumin levels and body weight. Levels of lipids and plasma proteins returned toward normal 2 weeks after injections were stopped. There was no difference in response between middle-aged and older animals. Conclusions. Chronic IL-6 injections cause acquired hypocholesterolemia, hypoalbuminemia, and weight loss in nonhuman primates. These changes are similar to those seen in older persons with acquired hypocholesterolemia.

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