Elevated levels of circulating interleukin-6 and transforming growth factor-β1 in patients with metastatic prostatic carcinoma

Purpose: Specific cytokines have been found to be secreted by and influence the growth of prostate cancers in cell culture. Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-beta 1 (TGF-beta 1) have all been closely associated with prostate cancer. We analyzed the levels of these cytokines in the systemic circulation of patients with varying stages of prostate cancer compared to controls. Materials and Methods: Serum IL-6, TNF alpha and GM-CSF were measured using commercially available enzyme linked immunosorbent assays in 5 groups of patients, including controls-19 men presenting to prostate cancer screening with normal digital rectal examination and serum prostate specific antigen (PSA) no greater than 2.0 ng./ml., stage pT2-19 with cancer confined to the prostate in the radical prostatectomy specimen, stage pT3-10 with extraprostatic extension and/or seminal vesicle involvement, stage N1-12 with lymph node metastases at pelvic lymph node dissection, and stage M1-9 with bone metastases. Platelet poor plasma TGF-beta 1 was measured using a commercially available enzyme linked immunosorbent assay in controls and patients with stage MI disease only because it was not available for patients with stages pT2, pT3 and NI disease. No patient had a history of any other malignancy. All blood specimens were collected before surgery and/or androgen ablation. Statistical analysis was done with the Kruskal-Wallis analysis of variance. Results: Serum IL-6 and platelet poor plasma TGF-beta 1 were significantly elevated in patients with clinically evident metastases (p = 0.0008 and 0.0412, respectively) while serum GM-CSF and TNF alpha were not. IL-6 and TGF-beta 1 correlated with increasing serum PSA (p = 0.0335 and 0.0386, respectively). GM-CSF did not correlate with PSA or age. In multivariate analysis TNF alpha correlated with age but not PSA. Conclusions: IL-6 and TGF-beta 1 correlate with tumor burden as assessed by serum PSA or clinically evident metastases. Further research is needed to determine the response to androgen ablation as well as the source(s) and actions of these cytokines.