Cytokine repertoire of epithelial cells lining the human urinary tract

PURPOSE: To examine the cytokine profile of epithelial cells lining the human urinary tract with the aim of differentiating between the constitutive and disease-related cytokine production in these tissues.

MATERIALS AND METHODS: Sections from the renal pelvis, ureter, bladder or urethra were obtained from 22 patients undergoing urinary tract surgery and were stained with monoclonal antibodies to interleukin(IL)-1beta, IL-4, IL-6, IL-8, interferon gamma (IFNgamma) and transforming growth factor beta (TGFbeta). Sections were classified according to the presence or absence of disease in the tissue.

RESULTS: Epithelial cells lining the renal pelvis, ureter, bladder or urethra all stained for IL-8 and TGFbeta (100%) in disease-free tissues and sections with cancer or interstitial cystitis (IC). In contrast, staining for IL-1beta, IL-4, IL-6 and IFNgamma varied with the disease state of the patient. Epithelial IL-1beta staining was absent (0%) in sections from healthy bladder, but positive in tissues with IC or cancer-associated pathology (50 to 100%). IL-6 staining was detected in the epithelial layer of several patients with IC or cancer related pathology, but only in cells with non-epithelial morphology and not in disease-free tissues. IFNgamma and IL-4 staining were only observed in patients with IC and only in cells with non-epithelial morphology.

CONCLUSIONS: The results show that epithelial cells from all parts of the urinary tract constitutively produce IL-8 and TGFbeta and suggest that the production of other cytokines varies with the disease of the patient. Constitutive cytokine production provides the basis for a rapid host response, in the defense against mucosal attack by microbes or toxic agents.