Cytokines Response after Intravesical Bacillus Calmette-Guerin(BCG) Therapy in Patients with Superficial Bladder Cancer

Kim, Sang Wan; Kim, Dal Sik; Kim, Hyung Jin

Abstract

PURPOSE: The mechanism by which BCG exerts its antitumor response in superficial bladder cancer is unclear but associated with T cell mediated immunity and cytokine production. The type 1 helper T cells(Th1) produce interleukin-2(IL-2) and interferon-gamma(IFN-gamma) while type 2 helper T cells (Th2) release interleukin-4(IL-4), interleukin-5(IL-5) and interleukin-10(IL-10). We measured cytokines(IL-12, IFN-gamma and IL-10) to determine if BCG induced the production of Th1 and Th2 cytokines from urine and serum. MATERIALS AND METHODS: In this study 10 patients with superficial bladder cancer(Ta, T1), 5 normal volunteers and 5 patients with cystitis were evaluated. Urine and serum were collected before BCG and during 4-6 hours after 5 or 6 consecutive weekly BCG instillations. The cytokines were measured by monoclonal ELISA assays. RESULTS: Urine and serum levels of IL-12, IFN-gamma and IL-10 were no difference between control groups(normal volunteers and cystitis patients) and pre-BCG bladder cancer patients. There were no apparent elevations of IFN-gamma and IL-10 levels in the sera following BCG therapy except for IL-12. In 8 patients following BCG therapy, IFN-gamma levels were significantly elevated in the urine compared to pre-BCG patients. IL-12 and IL-10 were also significantly increased in the urine in 7 and 6 patients respectively. Elevations of IFN-gamma in the urine correlated most with that of IL-12 and IL-10. CONCLUSIONS: Our results demonstrate that BCG can induce the production of Th1 and Th2 cytokines from urine and these cytokines may contribute to the antitumor immunity of BCG. However, further study is necessary to identify the correlation between change of these cytokines and clinical outcome such as recurrence or progression.