Interleukin-4 deficiency promotes gallstone formation.
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
Victoria L
VL
Gill Heart Institute, Division of Cardiovascular Medicine, Division of Hematology/Oncology, University of Kentucky, Lexington, KY 40536, USA.
Szilvassy
Stephen J
SJ
Daugherty
Alan
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000737:chemistry; D001663:Bilirubin / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002769:Cholelithiasis / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
D001798:Blood Proteins; D008055:Lipids; D011973:Receptors, LDL; D014280:Triglycerides; D015847:Interleukin-4; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin