The role of granulocytes following intravesical BCG prophylaxis.
OBJECTIVE
The antitumour effect of bacillus Calmette-Guérin (BCG) still remains relatively undefined. Most investigations on its mechanism of action have focused on mononuclear cells; little consideration has been given to granulocytes. We analysed urine of patients with bladder cancer during 8 wk of intravesical BCG prophylaxis. The number of polymorphonuclear neutrophils (PMNs) and urothelial cells (UCs) was evaluated. We examined the in vitro response of the T24 UC line to human PMNs after BCG treatment.


METHODS
Seventeen patients were enrolled in the study. Cytologic analyses were performed on urine samples collected before each BCG instillation and after 2 h from the first voided urine after BCG instillation. Elastase activity was determined on these samples to evaluate PMN activation. PMN-induced damage was measured on the T24 cell line treated with BCG.


RESULTS
After BCG treatment, a large number of PMNs transmigrated through the urothelium and PMNs adherent to detached UCs were found. One patient, who did not respond with significant PMN transmigration, experienced recurrent disease. The number of eosinophils that transmigrated was low, with the exception of three patients with recurrent disease. In vitro, PMNs adhered to BCG-primed T24 cells and damaged the monolayer.


CONCLUSIONS
The results agree with recent evidence that PMNs may play an important role in the antitumour action of BCG during the BCG induction period. This role is probably nonspecific because both normal UCs in vivo and tumour cells in vitro appeared to be injured. As suggested by results obtained from a limited number of patients, a high number of eosinophils in the urine may indicate therapy failure.
Siracusano
Salvatore
S
Department of Urology, Trieste University, Trieste, Italy. siracus@univ.trieste.it
Vita
Francesca
F
Abbate
Rita
R
Ciciliato
Stefano
S
Borelli
Violetta
V
Bernabei
Massimiliano
M
Zabucchi
Giuliano
G
D000283:Administration, Intravesical; D001500:BCG Vaccine / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000652:urine*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000628:therapy* / Q000652:urine*; D004591:Electrophoresis, Polyacrylamide Gel; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D049449:Luminescence; D016482:Urinalysis; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000652:urine*
D001500:BCG Vaccine; D014408:Biomarkers, Tumor