Cytokine variations in patients with hormone treated prostate cancer

J Urol. 2000 Sep;164(3 Pt 1):722-5. doi: 10.1097/00005392-200009010-00024.

Abstract

Purpose: We evaluated the immunological response in patients with hormone sensitive and refractory prostate cancer, and untreated benign prostatic hyperplasia (BPH).

Materials and 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / blood
  • Case-Control Studies
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Interferon-gamma / blood*
  • Interleukin-10 / blood
  • Interleukin-4 / blood
  • Interleukin-6 / blood
  • Interleukins / blood*
  • Male
  • Orchiectomy
  • Prognosis
  • Prostate-Specific Antigen / blood
  • Prostatic Hyperplasia / blood
  • Prostatic Hyperplasia / immunology
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology
  • Remission Induction
  • Tumor Necrosis Factor-alpha / analysis*

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Interleukin-6
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Gonadotropin-Releasing Hormone
  • Interferon-gamma
  • Prostate-Specific Antigen