Systemic and local immunomodulatory effects of intravesical BCG therapy inpatients with superficial urinary bladder carcinomas

Purpose: The aim of the present study was to elucidate whether only local, or also systemic immunomodulatory effects may be induced by intravesical BC G therapy of superficial urinary bladder cancer. Materials and Methods: A total of 37 patients with stages Ta to T1b superfi cial transitional cell bladder carcinomas received 6 weekly BCG instillatio ns after transurethral resection of the tumor. In a first group of 19 patie nts blood was taken before each BCG instillation and 6 weeks after the last one. In a second group of 18 patients blood and urine was taken before and 2, 6, and 24 hours after each BCG instillation. In the mitogen-stimulated whole blood cell cultures and in the urine samples the levels of the cytoki nes IL-1 beta, IL-2, IL-10, TNF-alpha and IFN-gamma were determined by enzy moimmunological tests. Additionally, in all plasma and urine samples the le vels of TNF-p75-receptor (TNF-p75-R) were measured. Results: Comparison of ex vivo leukocyte cytokine production in the blood c ell cultures of the patients of group I revealed no significant change in t he levels of the cytokines. In contrast, TNF-p75-R plasma levels increased significantly during the experimental time of 12 weeks (p less than or equa l to 0.01). In the blood cell cultures of the group II patients a different daytime var iation of cytokine production was seen, compared to the 19 healthy controls . After BCG instillation the normal peak cytokine production in the evening was suppressed. A significant rise in plasma TNF-p-75-R levels was measure d 24 hours after BCG instillation (p less than or equal to 0.05). In the ur ine of these patients significantly higher levels of all measured cytokines and TNF-p75-R were observed 6 to 24 hours after the instillation. Conclusions: The results suggest that besides the well known local immune a ctivation, BCG instillation also leads to a modulation of peripheral immune mechanisms.