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PMID:11971948

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Citation

King, VL, Szilvassy, SJ and Daugherty, A (2002) Interleukin-4 deficiency promotes gallstone formation. J. Lipid Res. 43:768-71

Abstract

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.

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Keywords

Alanine Transaminase/blood; Animals; Aspartate Aminotransferases/blood; Bile/chemistry; Bilirubin/metabolism; Blood Proteins/metabolism; Cholelithiasis/genetics; Cholesterol/metabolism; Interleukin-4/deficiency; Interleukin-4/genetics; Interleukin-4/physiology; Lipid Metabolism; Lipids/blood; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, LDL/deficiency; Receptors, LDL/genetics; Receptors, LDL/physiology; Triglycerides/metabolism

Significance

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Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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