Men with acute cholecystitis have higher tissue-based cytokine levels than women: A cross-sectional study

Aim. Sex-based differences in surgical outcomes may be related to socioeconomic, behavioral, or physiologic factors. Estrogenreceptor-related modulation is a proposed mechanism for sex-based differences in reaction to inflammation. We evaluated sex-based differences in gallbladder tissue-levels of inflammatory cytokines using a novel method to collect interstitial fluid from cholecystectomy samples. Methods. Patients undergoing laparoscopic cholecystectomy for acute or chronic cholecystitis were prospectively enrolled from August 1, 2006, through August 1, 2009. Immediately after gallbladder removal, interstitial fluid from the gallbladder fundus and infundibulum was collected. Tissue-level cytokines were determined using a multiplex cytometric bead assay. Messenger RNA levels of estrogen receptors and aromatase (ESR1, GPER, CYP19A1) were analyzed with real-time reverse transcriptasepolymerase chain reaction. Results. Interstitial fluid from gallbladder tissue of 78 patients (48 women) was analyzed. All patients with acute cholecystitis had higher levels of interleukin (IL)-6 and IL-10 than patients with chronic cholecystitis. Men with acute disease had higher tissue levels of IL-6 and IL-8 than women. IL-1β and IL-10 were increased only in men with acute cholecystitis. Tumor necrosis factor-α levels did not vary by sex or disease status. Tissues from acutely inflamed gallbladders had higher expression of a G protein-coupled estrogen receptor (GPER) and aromatase (CYP19A1). Conclusion. Tissue-level proinflammatory cytokines differ between men and women with acute cholecystitis. Mechanistic studies are needed to determine whether changes in cytokine levels or estrogen function contribute to local tissue inflammation and whether these influence surgical outcomes.