Presence of interleukin-2 in urine of superficial bladder cancer patients after intravesical treatment with bacillus Calmette-Guérin

Abstract

Urine samples were obtained from patients with superficial bladder cancer after immunotherapy with bacillus Calmette-Guérin (BCG). The patients were repeatedly (once a week for 6 consecutive weeks) treated with intravesical administration of approximately 5 × 10⁸ culturable particles of BCG. Some patients received more than six BCG instillations. The urine samples were investigated for the presence of interleukin-2 (IL-2) in an in vitro bioassay using a murine cytotoxic T cell line (CTTL-16) that shows IL-2-dependent growth. Preliminary experiments indicated the presence of inhibitory factors in the urine. This inhibitory activity was abolished after 24 h dialysis. In a neutralization assay with both polyvalent and monoclonal anti-(human IL-2) antibody it was demonstrated that there was indeed IL-2 in the urine samples. In 8 of 11 patients the presence of IL-2 in the urine was demonstrated. The IL-2 production was directly related to the BCG administration as samples obtained just before the BCG instillation were always negative. In IL-2-positive samples a maximum level of IL-2 was observed between 2 h and 6 h after the BCG instillation. In urine samples obtained 24 h after the BCG IL-2 was not detected. In most patients the urine became positive after the third or fourth BCG instillation