Localization of IL-1, IL-2, IL-4, IL-8 and TNF in Superficial Bladder Tumors Treated with Intravesical Bacillus Calmette-Guerin

Abstract

Cytokines have been detected in the urine during the first hours after intravesical Bacillus Calmette Guerin (BCG) treatment against superficial bladder cancer. To investigate the long-lasting mucosal inflammatory response, we analyzed intracellular cytokines by immunohistochemistry in biopsies taken 2 weeks after BCG treatment. Tumor biopsies were obtained from 8 patients with noninvasive, papillary transitional cell carcinoma (TCC), and intracellular cytokines were visualized by immunohistochemistry using cytokine-specific monoclonal antibodies. Interleukin (IL)-1 beta+ or tumor necrosis factor (TNF)-alpha+ cells were abundant in tumor and stroma. Interleukin-1 alpha, IL-2, IL-4, IL-8 and TNF-beta were variably expressed, while IL-10+ and interferon (IFN)-gamma+ cells were not detected. Among the few patients studied (5 responders and 3 nonresponders to BCG treatment) no single cytokine or cytokine profile was associated with clinical response to BCG therapy. We conclude that the in situ cytokine response after BCG treatment is highly complex, since cytokine profiles differed among the 8 patients investigated and between tumor and surrounding tumor-free mucosa. Further studies, investigating larger numbers of patients, is required to clarify whether cytokine profiles correlate with the clinical response to BCG.