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.—King, V. L., S. J. Szilvassy, and A. Daugherty. Interleukin-4 deficiency promotes gallstone formation. J. Lipid Res. 2002. 43: 768–771.
Highlights
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 To determine the effects of IL-4 on the atherogenic process, chimeric mice were created by the repopulation of C57BL/6 LDLrϪ/Ϫ mice with bone marrow cells derived from strain-matched C57BL/6 IL-4ϩ/ϩ or IL-4Ϫ/Ϫ mice
At 8 weeks, no deaths occurred in the LDLrϪ/Ϫ mice repopulated with wild-type bone marrow cells, while there was a 50% mortality in the group repopulated with IL-4Ϫ/Ϫ bone marrow cells
Summary
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؊/؊ deficiency increased serum concentrations of bilirubin following feeding a fat-enriched diet These studies revealed an unexpected finding that IL-4 deficiency predisposes to gallstone formation.—King, V. Diets enriched in cholesterol and cholate promote the development of atherosclerosis and the formation of gallstones in specific strains of mice [2, 3]. To further analyze the effect of enhanced gallstone formation in IL-4 deficient mice we used C57BL/6 IL-4Ϫ/Ϫ and IL-4ϩ/ϩ mice These studies provided the unexpected result that IL-4 deficiency markedly increased the formation of gallstones during the feeding of a diet that was enriched in cholesterol, saturated fat, and cholate
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