The inflammatory effects of crystalline cholesterol monohydrate in the guinea pig gallbladder in vivo

Background. The etiologic role of crystalline material in inflammatory arthritis is well established. The role of crystals in cholecystis is unclear. We hypothesized that crystalline cholesterol monohydrate stimulates guinea pig gallbladder inflammation in vivo. Methods. Crystalline cholesterol monohydrate, lipopolysaccharide (LPS), lysolecithin, polystyrene latex spheres (noninflammatory particles), and saline were instilled into guinea pig gallbladders for 24 to 72 hours after cystic duct ligation. Water transport across gallbladder mucosa was measured. Gallbladder tissue was analyzed for mucus layer thickness, myeloperoxidase, prostaglandin E-2(PGE(2)), prostaglandin F-1 alpha (PGF-1 alpha), and interleukin-1. Luminal fluid was also examined for PGE(2) and PGF-1 alpha. Values for each test were compared with saline controls by using Student's test (p < 0.05). Results. Crystalline cholesterol, LPS, and lysolecithin caused significant reduction in mucus layer thickness, reversed water absorption to secretion across the gallbladder mucosa, caused significant increases in myeloperoxidase and interleukin-1 in gallbladder tissue, and caused significant increases in PGE(2) and PGF-1 alpha in luminal fluid. These effects were generally dose- but not time-dependent. Polystyrene latex particles caused no difference in outcomes compared with saline controls. Conclusions. Crystalline cholesterol monohydrate has dose-dependent inflammatory effects in the guinea pig gallbladder in vivo that are not simply due to mechanical irritation of the gallbladder wall by crystalline particles. Crystals in the gallbladder may have an etiologic role in cholecystitis.