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.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Expression of phenotypic markers of mast cells, macrophages and dendritic cells in gallbladder mucosa with calculous cholecystitis.

The study aimed at quantitative analysis of expression involving markers of mast cells (tryptase), monocytes/macrophages (CD68 molecule) and dendritic cells (S100 protein) in gallbladder mucosa with acute and chronic calculous cholecystitis. Routinely prepared tissue material from the patients with acute (ACC) (n = 16) and chronic calculous cholecystitis (CCC) (n = 55) was evaluated. Three cellular markers were localized by immunocytochemistry. Their expression was quantified using spatial visualization technique. The expression of tryptase was similar in acute and chronic cholecystitis. CD68 expression in ACC was significantly higher than in the CCC group. Expression of S100 protein was significantly higher in CCC as compared to the ACC group. No significant correlations were disclosed between expression of studied markers and grading in the gallbladder wall. A weak negative correlation was noted between expression of CD68 and number of gallstones in the CCC group. The spatial visualization technique allowed for a credible quantitative evaluation of expression involving markers of mast cells (MCs), monocytes/macrophages (Mo/Ma) and dendritic cells (DCs) in gallbladder mucosa with ACC and CCC. For the first time mucosal expression of S100 protein-positive DCs was evaluated in calculous cholecystitis. The results point to distinct functions of studied cell types in the non-specific immune response in calculous cholecystitis.

Cellular expression of interleukin 2 (IL-2) and its receptor (IL-2R, CD25) in lung tumours.

In view of the unclear prognostic and diagnostic role of interleukin 2 (IL-2) and its receptor in human tumours, we examined the cellular expression of IL-2 and of the subunit alpha of its receptor (IL-2Ralpha, CD25) in relation to the proliferative activity of various subtypes of lung tumours. The immunocytochemical ABC technique was applied to archival tissue material of neuroendocrine lung tumours: lung carcinoids, including typical carcinoids (TC), atypical carcinoids (AC) and small-cell lung cancers (SCLC) and squamous cell lung cancers (non-small cell lung cancers, NSCLC). Expression of IL-2 was detected in all types of lung tumours. The highest frequency of IL-2 expression (93%) was noted and the most pronounced semi-quantitatively evaluated expression of IL-2 was detected in AC tumour cells. The expression was more pronounced as compared to neoplastic SCLC (p = 0.01) and NSCLC cells (p = 0.005). The results suggest a negative correlation between IL-2 expression and the proliferative activity of tumour cells (evaluated by expression of Ki-67) in AC. The frequency of detection of IL-2 receptor (IL-Ralpha, CD25) was the highest in NSCLC (94%). Semi-quantitative expression of IL-2R, like that of IL-2, also dominated in the group of atypical lung carcinoids but manifested a significant difference only as compared to typical carcinoids (p = 0.014). Within the groups of tumours studied no correlation could be detected between cellular expressions of IL-2 and IL-2R. Our results demonstrate variable expression of IL-2 and its receptor in various types of lung tumours, but no simple relationship could be detected between tissue expression of the markers and proliferative activity. Appraisal of the diagnostic and/or prognostic significance of the results requires further study.