Elevation of cytokine levels in cachectic patients with prostate carcinoma

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Abstract
BACKGROUND Approximately 60–70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor α (TNFα) and interleukin 1 (IL‐1), IL‐6, and IL‐8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFα, IL‐1β, IL‐6, and IL‐8. METHODS The levels of TNFα, IL‐1β, IL‐6, IL‐8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ‐confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total‐PSA assays were used to determine cytokine and PSA levels, respectively. RESULTS Levels of TNFα, IL‐6, and IL‐8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFα were correlated positively with IL‐8, and there was no correlation between PSA levels and any of the cytokine levels. IL‐1β levels were below the limit of detection in all samples. CONCLUSIONS The current results show that levels of TNFα, IL‐6, and IL‐8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia. Cancer 2003;97:1211–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11178