title: Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette-Guérin immunotherapy for carcinoma in situ of the bladder.
abstract: OBJECTIVE
  The mechanism by which bacillus Calmette-Guérin (BCG) mediates antitumor activity has not been clearly established. Specific cytokines in the urine after BCG intravesical instillation therapy may serve as a prognostic factor of treatment response. In this study, various urinary cytokines such as interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8. IL-10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured.
  
  
  METHODS
  In total 20 patients were treated with BCG intravesical instillation therapy for carcinoma in situ of the bladder. At the completion of the first and eighth instillations, spontaneously voided urine specimens were collected before BCG instillation, every 2 h until 12 h, and thereafter until 24 h. All specimens were ultrafiltrated using an ADVANTEC UK-10 membrane. The cytokines were measured using ELISA and RIA techniques.
  
  
  RESULTS
  Significantly higher levels of IL-2, IL-6, IL-8, IL-10, IFN-gamma, and TNF-alpha were detected in the eighth instillation as compared to the first instillation ( p<0.001). After BCG intravesical instillation therapy, treatment failure occurred in 6 of the 20 patients (30%), including primary failure (persistence of CIS) in 3, and de novo failure (tumor recurrence) in 3 with a median follow-up of 46.9 months. Significantly higher production of IL-2, IL-6, IL-8, IL-10, and TNF-alpha was observed in the responder group than in the non-responder group ( p<0.05). Multivariate analysis revealed IL-2 as an independent prognostic cytokine of responder status.
  
  
  CONCLUSIONS
  This study indicates that urinary IL-2 at the eighth instillation of BCG may serve as a valuable prognostic factor of treatment efficacy as well as tumor recurrence after treatment.
authors.affiliation: Department of Urology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi Ube, 755-8505, Yamaguchi, Japan.
authors.forename: Etsuya
authors.initials: E
authors.lastname: Watanabe
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Chietaka
authors.initials: C
authors.lastname: Ohmi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Tei
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshihiro
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Naito
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000652:urine; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000652:urine; D016022:Case-Control Studies; D016207:Cytokines / Q000652:urine; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000628:therapy / Q000652:urine; D009367:Neoplasm Staging; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000652:urine
chemical_list: D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha