Analysis of immunohistochemical expression of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in gallbladder mucosa: comparative study in acute and chronic calculous cholecystitis

Several studies have shown increased serum levels of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in patients with cholelithiasis. The local expression of the proteins involved in pathogenesis of the disease is poorly recognised.The authors examined immunohistochemically (IHC) the expression status of IL-1α, IL-6, and TNF-α in gallbladder mucosa of the patients with cholelithiasis as related to acute (ACC) and chronic (CCC) types of cholecystitis. Proinflammatory cytokines were quantitatively evaluated in gallbladder mucosa (epithelium and lamina propria) in ACC (n = 16) and CCC (n = 55) groups using modern spatial visualisation technique.Quantitative analysis of IHC signals showed no significant differences in IL-1α and IL-6, and immunoexpression in patients with ACC and CCC. A significantly greater IHC expression of TNF-α was detected in CCC as compared with ACC group. In either of the patient groups immunoexpression of IL-1α and of TNF-α was significantly higher than that of IL-6. Immunoexpression of TNF-α was significantly higher than that of IL-1α only in CCC group. A positive correlation was disclosed between IHC expression of IL-1α and body mass index in CCC group. IHC expression of TNF-α correlated positively with expression of CD68 molecule (histiocytic marker), number of leukocytes in blood and higher grading of gallbladder wall in ACC group.A more pronounced IHC expression of TNF-α and IL-1α than IL-6 in both types of cholecystitis may suggest the role of these cytokines in pathogenesis of cholelithiasis. IHC expression of TNF- α shows better correlation with clinical/laboratory data in acute cholecystitis, and its quantitative prevalence over the remaining cytokines points to the role of the TNF-α in maintenance of inflammation in the course of cholelithiasis.