title: Cytokine variations in patients with hormone treated prostate cancer.
abstract: OBJECTIVE
  We evaluated the immunological response in patients with hormone sensitive and refractory prostate cancer, and untreated benign prostatic hyperplasia (BPH).
  
  
  METHODS
  Serum levels of pro-inflammatory and anti-inflammatory cytokines were measured by enzyme-linked immunosorbent assay in 3 groups of patients. The groups included 18 men with a mean age of 79 years who had hormone sensitive prostate cancer, mean prostate specific antigen (PSA) plus or minus standard deviation 1.03 +/- 2.65 ng./ml. and a mean of 35 months of treatment, 10 with a mean age of 86 years who had hormone refractory prostate cancer, mean PSA 27.52 +/- 42.23 ng./ml. and a mean of 42 months of treatment, and 19 with a mean age of 73 years who had BPH and mean PSA 3.37 +/- 2.47 ng./ml. Results were compared with those in 10 age matched, disease-free controls. In the hormone sensitive group PSA regressed to normal and there was clinical evidence of a response to hormone ablation therapy, including orchiectomy, luteinizing hormone releasing hormone analogue and androgen blockade. Hormone refractory cases had elevated PSA and/or clinical evidence of disease progression.
  
  
  RESULTS
  Levels of the anti-inflammatory cytokines interleukin (IL)-4, IL-6 and IL-10 were significantly elevated in the hormone refractory group compared with values in the hormone sensitive group (p = 0.02, 0.01 and 0.0001, respectively). Abnormal anti-inflammatory cytokines in hormone resistant cases correlated with elevated PSA, while in the BPH group there was no significant difference from controls. Pro-inflammatory cytokines in the hormone sensitive and resistant groups were not significantly different from those in controls.
  
  
  CONCLUSIONS
  Our study indicates that in hormone refractory prostate cancer a high level of the anti-inflammatory cytokines IL-4, IL-6 and IL-10 develops that is directly associated with elevated PSA. Changes in the level of anti-inflammatory cytokines when androgen independent cells exist may have an important role in the selection of a subset of hormone insensitive cells. These criteria may be used as a prognostic marker for the response to hormone ablation therapy in men with prostate cancer.
authors.affiliation: Divisions of Urology and Urological Research, Maimonides Medical Center, Brooklyn, NY, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Wise
authors.forename: V K
authors.initials: VK
authors.lastname: Marella
authors.forename: G
authors.initials: G
authors.lastname: Talluri
authors.forename: D
authors.initials: D
authors.lastname: Shirazian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008297:Male; D009919:Orchiectomy; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007987:Gonadotropin-Releasing Hormone; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen