Detection of interleukin 2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG

Abstract

Adjuvant intravesical BCG therapy is an effective means of treating superficial bladder tumors. The mechanism by which BCG mediates antitumor activity is not known; however, clinical and animal studies suggest that immunological responsiveness to BCG antigens correlates with antitumor activity. In this report the detection of interleukin 2 (IL-2, a lymphokine produced in response to BCG) in urine specimens of patients treated with intravesical BCG is reported. Patients with superficial transitional cell carcinoma of the bladder received intravesical BCG once each week for six weeks. No intradermal injections were administered. Urine specimens were obtained prior to BCG instillation and four, eight and 24 hours afterwards. The specimens were dialysed, concentrated five-fold and assayed for the presence of IL-2 in a biological assay using an IL-2 dependent cultured T-cell line. IL-2 was detected in urine but not serum after intravesical BCG instillation. IL-2 was characterized by absorption against an IL-2-dependent T cell line and neutralization by monoclonal anti-IL-2 antibodies. No IL-2 was detected in specimens obtained prior to BCG instillation or from donors with no detectable bladder pathology. One of 10 urine specimens from patients with urinary tract infections had detectable IL-2 levels. IL-2 production generally peaked during the fourth to sixth intravesical BCG treatment. Production was short-term in that IL-2 levels peaked four to eight hours after BCG instillation and were rarely (six of 54 specimens) observed 24 hours after instillation. Mean IL-2 levels were higher in patients who were rendered tumor free after BCG therapy but statistical significance was not achieved. Ten of 12 patients (83%) who responded to BCG therapy had urine IL-2 levels greater than or equal to 1.6 units/ml. at least once during the six week treatment period while two of six (33%) patients not responding to therapy had similar urine IL-2 levels. These results show that intravesical BCG therapy induces the production of lymphokines including IL-2. The presence of BCG-induced lymphokines may be associated with anti-tumor activity.