Variation of the immunosystem by ciclosporin and keyhole-limpet hemocyanin--are there effects on chemically induced bladder carcinoma?

Ciclosporin (CsA) and keyhole-limpet hemocyanin (KLH) are potent immunomodulators. Their effects on the induction of bladder carcinoma were investigated in Wistar rats using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as a known initiator of bladder carcinoma. In a first series the immunosystem was suppressed by CsA. Rats treated with 0.05% BBN + CsA 5 mg/kg/day or CsA 12.5 mg/kg/day orally developed a CsA dose-dependent (2- to 4-fold) enhancement of bladder tumor expansion as compared to 0.05% BBN application alone. In contrast, immunovariation by stimulation with KLH 12.5 mg i.ves. + 0.5 mg s.c. 2 X/week after being sensitized with 1 X 1 mg KLH s.c. resulted in a reduction of BBN-induced bladder tumors. The results confirm the immunosurveillance theory that effective expression of immunoresponse may be important in the control of tumor development. The effective immunostimulation by KLH support the concept of immunotherapy in bladder cancer.