T helper 1/2 lymphocyte urinary cytokine profiles in responding and nonresponding patients after 1 and 2 courses of bacillus Calmette-Guerin for superficial bladder cancer

Purpose: Interleukin (IL)-2 and interferon-gamma are released during T help er 1 lymphocyte responses and IL-10 is released during T helper 2 lymphocyt e responses. We have previously reported that a T helper 1 lymphocyte urina ry cytokine profile is associated with a favorable prognosis after bacillus Calmette-Guerin (BCG) treatment. We evaluated the T helper 1/2 lymphocyte cytokine profiles during courses 1 and 2 of 6 weekly BCG instillations. Materials and Methods: Urinary interferon-gamma, IL-2 and IL-10 were measur ed by enzyme-linked immunosorbent assay after each of 6 weekly instillation s of 150 mg. BCG, Pasteur strain, in 19 patients with superficial stages Ta and T1 bladder cancer, and carcinoma in situ. The 11 patients who did not respond to course 1 were re-treated according to the same schedule and reev aluated. Results: During course 1 interferon-gamma was higher than during course 2 ( p <0.001), which was associated with nonrecurrence (p <0.001). In contrast, IL-2 cytokine was higher after course 2 (p <less than>0.01), which was ass ociated with a BCG response (p = 0.01). Interferon-gamma and IL-10 correlat ed during courses 1 and 2 (p = 0.04 and 0.0004, respectively). We distingui shed groups 1-immediate T helper 1 lymphocyte profile consisting of respond ers to course 1 with high interferon-gamma, IL-2 and IL-10, 2-delayed T hel per 1 lymphocyte profile consisting of responders to course 2 with early hi gh IL-2 and 3-consisting of nonresponders to the 2 courses with low interfe ron-gamma, IL-2 and IL-10. Conclusions: A T helper 1 lymphocyte urinary cytokine profile was associate d with a clinical response to BCG. A repeat BCG course induces a favorable immune response in a subset of patients, suggesting that maintenance therap y may be beneficial.