Interleukin-6 production by bladder tumors is upregulated by BCG immunotherapy.
OBJECTIVE
To determine whether BCG therapy could upregulate interleukin-6 (IL-6) production in human transitional cell carcinomas (TCC).


METHODS
Immunohistochemistry of tumor biopsies and urinary cytospins and ELISA studies of urine from bladder cancer patients and TCC cell-line supernatants, before and after exposure to BCG, were performed.


RESULTS
Constitutive staining for IL-6 was found in the majority of bladder tumors. Interleukin-6 was detected in the urine of all 13 patients with carcinoma in situ and increased 5-fold during BCG therapy. Levels were variable but were greater in nonresponders (p < 0.01). During therapy both detached bladder urothelial cells and polymorphonuclear leukocytes stained for IL-6. Production of IL-6 increased in only 3 cell lines after exposure to BCG, but all 7 cell lines showed increases after exposure to interferon-gamma (p = 0.015). Grade 3 cell lines showed much greater upregulation than grade 1 and 2 cell lines.


CONCLUSIONS
The increase in IL-6 during BCG therapy may be caused by urothelial cells as well as leukocytes. The higher levels seen in nonresponders may be due to either higher grade or persisting tumor.
Esuvaranathan
K
K
Department of Surgery, National University of Singapore.
Alexandroff
A B
AB
McIntyre
M
M
Jackson
A M
AM
Prescott
S
S
Chisholm
G D
GD
James
K
K
D001500:BCG Vaccine / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000628:therapy; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000628:therapy
D001500:BCG Vaccine; D015850:Interleukin-6; D007371:Interferon-gamma