CHANGES IN URINARY CYTOKINES AND SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IN BLADDER-CANCER PATIENTS AFTER BACILLUS-CALMETTE-GUERIN (BCG) IMMUNOTHERAPY

Intravesical immunotherapy for carcinoma in situ of the bladder is arg uably the most effective form of tumour immunotherapy described to dat e. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients' urine. This s tudy concerns the production of IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL- 10, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-ga mma) and soluble ICAM-1 (sICAM-1) throughout the six weekly instillati ons which comprise a therapeutic course. Sequential instillations of B CG induced secretion of IL-1 beta, IL-2, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and sICAM-1 into urine. The responses were heterogeneous be tween patients and cytokines, but some general trends were evident. Al though cytokine levels were initially low, their concentration increas ed with repeated instillation of BCG. Certain cytokines (e.g. IL-6, IL -8 and IL-10) could be detected after the first instillation, whilst o thers (e.g. IL-2 and IFN-gamma) were not detected until after the thir d or fourth instillation. Interestingly, IL-4 was not detected, perhap s suggesting a differential effect on Th2-like responses. Some patient s produced particularly elevated or non-detectable levels of cytokines , and a positive correlation was found between the production of vario us cytokines. The production of a particular cytokine did not correspo nd with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value w ill be determined in a larger series of patients. However, as these po tent immunomodulators are thought to be important for the 75% complete clinical response observed with BCG therapy, there remains the possib ility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary f orerunner to full prognostic evaluation of such immunological data.