Immunomodulatory Tissue Factors in the Gallbladder Walls of Pediatric Patients with Chronic Calculous Cholecystitis

TL;DR

This study investigates immune-related factors in the gallbladder walls of children with chronic gallbladder inflammation, revealing key differences compared to healthy tissue.

Contribution

The study identifies specific immunomodulatory factors and their roles in pediatric chronic calculous cholecystitis.

Findings

IL-1β, SHH, and NFkBp65 showed significant differences in epithelial expression between patient and control samples.

IL-12, SHH, and HSP60 were more prominently expressed in blood vessels of patient gallbladders.

Positive correlations among the studied factors suggest coordinated immune modulation in disease progression.

Abstract

Background: The rising rates of gallstones and cholecystectomy in pediatric populations underscore the increasing concern regarding chronic cholecystitis. However, the morphopathogenesis of pediatric calculous cholecystitis is still not well understood. This study aimed to determine the expression and distribution of immunomodulatory factors interleukin-12 (IL-12), interleukin-13 (IL-13), interleukin-1β (IL-1β), sonic hedgehog protein (SHH), nuclear factor NF-kappa-B p65 subunit (NFkBp65), and heat shock protein 60 (HSP60) in the gallbladder walls of pediatric patients with chronic calculous cholecystitis. Methods: In total, 11 gallbladder samples were collected from pediatric patients with calculous cholecystitis during cholecystectomy, while 5 healthy gallbladder samples served as controls. IL-12, IL-13, IL-1β, SHH, NFkBp65, and HSP60 were detected by immunohistochemistry. The number of positive structures in gallbladder wall epithelium, vasculature, and inflammatory infiltrate was assessed semi-quantitatively by microscopy. A Mann–Whitney U test and Spearman’s rank-order correlation coefficient were calculated. Results: Statistically significant differences were observed between patient and control samples in the expression of IL-1β, SHH, and NFkBp65 in the epithelium, as well as in the expression of IL-12, SHH, and HSP60 in the blood vessels. The expression of IL-1β was stronger in the epithelium of controls, while other markers were more prominent in patient samples. Conclusions: An increased number of NFkBp65, IL-12, and HSP60 positive cells in patient gallbladder tissue suggests a significant role of these tissue factors in driving immune modulation and sustaining the inflammation in pediatric chronic calculous cholecystitis. The noticeable expression of SHH in patient gallbladder tissue indicates its part in tissue regeneration and repair processes, as well as in modulating inflammation and vascular responses in calculous cholecystitis. The significant positive correlations between the factors studied highlight the importance of their coordinated interaction and intricate crosstalk in the morphopathogenesis of calculous cholecystitis.

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