Interleukin-4 deficiency promotes gallstone formation

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.

Keywords

• bone marrow transplant
• LDL receptor
• cholesterol