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 poss ible treatment for decreasing tumor recurrence after transurethral res ection (TUR) in patients with superficial transitional cell carcinoma of the bladder (stages pTa-pT1, grades 1-3). Our study confirms the th eory that instillation of KLH stimulates production of cytokines, resu lting in their secretion in urine. Interleukin-l (IL-1) stimulates the immune cascade through a domino effect and is produced mainly by acti vated 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 immunoso rbent assay (ELISA) was used for analysis. The ELISA for IL-1 alpha wa s established in our laboratory and showed a detection limit of 5 pg/m l. This IL-1 alpha ELISA deviation amounts to 3-7% within a series of measurements, and 5-1 5% from series to series. In the therapy group t he IL-1 alpha secretion ranged from 0 to 30,905 pg/24 h and in the con trol group from 0 (collection period) to 2,472 pg/4h.IL-1 alpha produc tion increased significantly after KLH instillation in bladder cancer patients; however, the level varied considerably from patient to patie nt. Maximum production was achieved within a period of 4-8 h, decreasi ng 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 t hat of the KLH group. 8 of 14 patients (57%) who responded to KLH ther apy had higher urine IL-1 alpha la levels after 6 weeks of KLH treatme nt than those who failed to respond within 12 months, but the levels w ere not of statistical significance. The secretion of IL-lcr in urine is the biological response of the bladder to the antigen stimulus of K LH. No IL-2 was detected in the urine samples. It remains to be determ ined whether no IL-2 cytokine was present, or whether the amount was s maller than the minimal detection limit required for the ELISA.