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Journal of Lipid Research, Vol. 43, 768-771, May 2002
Copyright © 2002 by Lipid Research, Inc.

Interleukin-4 deficiency promotes gallstone formation

Victoria L. King^*, Stephen J. Szilvassy and Alan Daugherty^1,*

^* Gill Heart Institute, Division of Cardiovascular Medicine
Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Kentucky, Lexington, KY 40536

¹ To whom correspondence should be addressed. e-mail: adaugh{at}uky.edu

Manuscript received 17 May 2001, in revised form 16 January 2002, and in re-revised form 14 February 2002.

Feeding interleukin-4 (IL-4) deficient C57BL/6 LDL receptor (LDLr)^-/- mice a modified diet to investigate the role of this cytokine in cholesterol metabolism led to an unexpected phenotype. IL-4^-/- LDLr^-/- mice had enlarged gallbladders and an increased mortality that was preceded by acute body weight loss. To determine if IL-4 deficiency accounted for these findings, C57BL/6 IL-4^+/+ and IL-4^-/- mice were fed either a normal or modified diet. IL-4 deficiency did not alter bile composition or cause liver toxicity in mice fed a fat-enriched diet. Following 8 weeks of feeding a fat-enriched diet, no gallstones were detected in IL-4^+/+ mice, and only 20% had cholesterol crystals. In contrast, IL-4^-/- mice had a 100% incidence of gallstones and cholesterol crystals. IL-4^-/- deficiency also increased serum concentrations of bilirubin following feeding a fat-enriched diet. Therefore, these studies revealed an unexpected finding that IL-4 deficiency predisposes to gallstone formation.—King, V. L., S. J. Szilvassy, and A. Daugherty. Interleukin-4 deficiency promotes gallstone formation. J. Lipid Res. 2002. 43: 768–771.

Abbreviations: IL-4, interleukin-4; A:G, albumin/total protein; GOT: GPT, glutamic oxalacetic transaminase/glutamic pyruvic transaminase

Supplementary key words bone marrow transplant • LDL receptor • cholesterol

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