title: Interleukin-6 production by bladder tumors is upregulated by BCG immunotherapy.
abstract: 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.
authors.affiliation: Department of Surgery, National University of Singapore.
authors.forename: K
authors.initials: K
authors.lastname: Esuvaranathan
authors.forename: A B
authors.initials: AB
authors.lastname: Alexandroff
authors.forename: M
authors.initials: M
authors.lastname: McIntyre
authors.forename: A M
authors.initials: AM
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Prescott
authors.forename: G D
authors.initials: GD
authors.lastname: Chisholm
authors.forename: K
authors.initials: K
authors.lastname: James
mesh_terms: 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
chemical_list: D001500:BCG Vaccine; D015850:Interleukin-6; D007371:Interferon-gamma