Inflammation and a thickened mucus layer in mice with cholesterol gallstones

Background. Based on previous work which suggested that biliary crystals may induce inflammation in the gallbladder wall and that inflammation is an early event during the formation of pigment gallstones in the dog, studies were performed examining mucus layer thickness, myeloperoxidase activity, and interleukin-l (IL-1) activity in the wall of mouse gallbladder during formation and growth of cholesterol gallstones. Methods and Materials. The inflammatory effects of cholesterol gallstones at 2 and 4 weeks were studied in BalB/C mice fed a crushed standard mouse chow with added cholesterol (1.0%) and cholic acid (0.5%). Results were compared to those of normal mice fed standard mouse chow. The presence or absence of crystals and stones was determined by gross and microscopic examination of bile. Myeloperoxidase and IL-1 activity in the gallbladder wall was measured using well-established bioassays. Mucus layer thickness was measured by darkfield microscopy. Results. All mice fed a lithogenic, 1.0% cholesterol/0.5% cholic acid diet developed cholesterol crystals and gallstones at 2 and 6 weeks. No control mice developed either crystals or gallstones. Myeloperoxidase and IL-1 activities, markers of an inflammatory response, increased significantly in the gallbladder of mice with crystals at 2 weeks. Myeloperoxidase activity increased two-to three-fold, and IL-1 activity sevenfold, by 6 weeks. Mucus layer thickness also progressively increased during the 6-week period. Conclusions. It is concluded that inflammation is an early event associated with the appearance of crystals and gallstones in bile. (C) 1998 Academic Press.