A disproportion of TH1/TH2 cytokines with predominance of TH2, in urothelial carcinoma of bladder.

Bladder cancer is a common tumor of the urinary tract, accounting for 6% to 8% of all male malignancies and 2% to 3% of all female malignancies. Urothelial carcinoma (UC) of bladder is the second most common urologic malignancy after prostate cancer. Earlier report has elucidated immunologic unreactivity in cancer patients. Cytokines play a pivotal role in the induction of cell mediated and humoral immunity. Quantification of cytokine response in cancer patients can give significant insights about the cellular immunologic potency against the neoplastic cells. In the present study, we aimed to assess alterations of Th1 and Th2 derived cytokines in progression of UC of bladder by determining their circulatory concentration in bladder cancer patients and healthy controls and to correlate the observations with grade and severity of the disease. The study cohort consisted of 122 subjects; 72 patients with bladder UC (28, low grade; 17, high grade; 27, muscle invasive) and 50 healthy controls. The circulatory levels of various cytokines were measured using commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit from BD Biosciences, San Diego, CA, and were statistically correlated according to the grade and the severity of disease. The serum levels of typical Th1 cytokines: IL-2 and IFN-γ were found to be significantly lower (P < 0.001) while levels of Th2 cytokines i.e., IL-4, IL-5, and IL-10 were significantly higher (P < 0.001) in patients than in controls. The levels of all the cytokines were correlated with the grade and severity of the disease. There were significant differences between the patients with low grade tumors and muscle invasive tumors for all cytokines (P < 0.001); except IL-10 (P < 0.626). The results of our study delineate that in bladder tumor patients a marked polarization exists towards the expression of Th2 type cytokines while Th1 remain suppressed. Furthermore, the levels of all the cytokines alter according to the grades of the tumor. This can give significant insights about the use of Th1 type cytokines for the administration of immunotherapy to bladder cancer patients. Development of new strategies attempting to manipulate the equilibrium between Th1 and Th2 cells would be beneficial in the management of UC of bladder in future.