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Acute Dyslipoproteinemia Induced by Interleukin-2: Lecithin:Cholesteryl Acyltransferase, Lipoprotein Lipase, and Hepatic Lipase Deficiencies¹

Veterans Affairs Medical Center and the Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes and the Division of Hematology and Oncology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132; and University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4

Address all correspondence and requests for reprints to: Dana E. Wilson, M.D., Veterans Administration Hospital (111E), 500 Foothill Drive, Salt Lake City, Utah 84148. E-mail: minerals{at}xmission.com

Abstract

Recombinant human interleukin-2 (rIL-2) is used to treat refractory cancers. During such treatment, patients develop severe hypocholesterolemia along with striking alterations in the concentration and composition of the circulating lipoproteins. The present study was undertaken to gather information about the pathogenesis of these abnormalities. Patients were studied before-, during- and after a 5-day course of high dose iv rIL-2.

Whole plasma cholesterol was markedly reduced by rIL-2 administration (52%; P < 0.001), whereas the triglyceride concentration did not change. Thus, the lipoproteins became triglyceride enriched (P = 0.004). Low density lipoprotein cholesterol, apolipoprotein B (apoB), high density lipoprotein cholesterol, and apoA-I concentrations all decreased. Esterified cholesterol levels were markedly reduced. Total plasma apoE increased markedly, and two kinds of abnormal particles appeared: 1) ß-migrating, very low density lipoproteins; and 2) discoidal, apoE- and phospholipid-containing particles with abnormal density and electrophoretic mobility. The activities of two lipoprotein triglyceride hydrolases, lipoprotein lipase and hepatic lipase, fell significantly during treatment and returned promptly to pretreatment levels after rIL-2 was discontinued. Lecithin:cholesteryl acyltransferase (LCAT) activity also decreased significantly (64%) during treatment, but in contrast to the lipases, remained low for at least 5 days after the last dose of rIL-2 (P < 0.001).

High dose iv rIL-2 induces severe dyslipidemia with deficiencies of both postheparin lipases and acute LCAT deficiency. Most, if not all, of the lipoprotein changes observed are explained by the LCAT deficiency that follows IL-2-induced hepatocellular injury and cholestasis.

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