Urinary interleukin-1 alpha levels are increased by intravesical instillation with keyhole limpet hemocyanin in patients with superficial transitional cell carcinoma of the bladder.

Intravesical instillation of keyhole limpet hemocyanin (KLH) is a possible treatment for decreasing tumor recurrence after transurethral resection (TUR) in patients with superficial transitional cell carcinoma of the bladder (stages pTa-pT1, grades 1-3). Our study confirms the theory that instillation of KLH stimulates production of cytokines, resulting in their secretion in urine. Interleukin-1 (IL-1) stimulates the immune cascade through a domino effect and is produced mainly by activated macrophages. The instillation program was started 5-7 days after TUR of primary superficial cell carcinoma. 20 mg KLH in 20 ml of 0.9% NaCl was instilled into the bladder each week for 6 consecutive weeks and then monthly for 1 year. When KLH is instilled into the bladder, IL-1 alpha is secreted in the urine. A specific enzyme-linked immunosorbent assay (ELISA) was used for analysis. The ELISA for IL-1 alpha was established in our laboratory and showed a detection limit of 5 pg/ml. This IL-1 alpha ELISA deviation amounts to 3-7% within a series of measurements, and 5-15% from series to series. In the therapy group the IL-1 alpha secretion ranged from 0 to 30,905 pg/24 h and in the control group from 0 (collection period) to 2,472 pg/4 h. IL-1 alpha production increased significantly after KLH instillation in bladder cancer patients; however, the level varied considerably from patient to patient. Maximum production was achieved within a period of 4-8 h, decreasing within 24 h. There was a striking difference between the amount of IL-1 alpha produced over the 24-hour period in the control group and that of the KLH group. 8 of 14 patients (57%) who responded to KLH therapy had higher urine IL-1 alpha levels after 6 weeks of KLH treatment than those who failed to respond within 12 months, but the levels were not of statistical significance. The secretion of IL-1 alpha in urine is the biological response of the bladder to the antigen stimulus of KLH. No IL-2 was detected in the urine samples. It remains to be determined whether no IL-2 cytokine was present, or whether the amount was smaller than the minimal detection limit required for the ELISA.