CYTOKINE VARIATIONS IN PATIENTS WITH HORMONE TREATED PROSTATE CANCER

Abstract

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