Elevations of Cytokines Interleukin-1, Interleukin-2 and Tumor Necrosis Factor in the Urine of Patients after Intravesical Bacillus Calmette-Guerin Immunotherapy

Abstract

In an attempt to elucidate further the immunological mechanisms responsible for the effectiveness of intravesical bacillus Calmette-Guerin in the therapy of superficial urothelial bladder cancer, a prospective study was performed in which the urine of patients was examined before and after 6 intravesical instillations of bacillus Calmette-Guerin for the presence of the cytokines interleukin-1, interleukin-2 and tumor necrosis factor-alpha. Biological assays such as specific sandwich enzyme-linked immunosorbent assays were used for the analysis of each cytokine. Urinary titers of interleukin-1, interleukin-2 and tumor necrosis factor increased significantly after bacillus Calmette-Guerin instillation but showed inter-individual differences. The maximum of secretion into the urine was seen between 4 and 8 hours after the instillation, and titers returned to baseline values within 24 hours. The differences in 24-hour secretion between the bacillus Calmette-Guerin-treated (10 patients) and the control (10) groups were significant with respect to all cytokines as tested in both assays each, except for the interleukin-1 biological assay. These results reflect the strong inflammatory response in the bladder wall to bacillus Calmette-Guerin, in which the urinary secretion of the detected cytokines may be associated with the local tumor control.