Circulating Cytokine Levels in Prostate Cancer Patients Undergoing Radiation Therapy: Influence of Neoadjuvant Total Androgen Suppression

Background: The purpose of this study was to investigate the immunological impact of combining neoadjuvant total androgen suppression (TAS) with radiotherapy (xRT) in the treatment of prostate cancer by monitoring blood cytokine levels. Patients and Methods: Participants were stage I-II prostate cancer patients receiving xRT alone (n=18) or TAS+xRT (n=19) under the procedures outlined in RTOG protocols #94-08 and #94-13. Peripheral blood samples were collected immediately prior to TAS (xRT+TAS group), immediately, prior to xRT, 24 hours after initiation of xRT, and weekly, during xRT. Samples were monitored for the immunoregulatory cytokines interleukin (IL)-1 beta, IL-6 and transforming growth factor (TGF)beta using ELISA procedures. Results: Following initiation of xRT, both patient groups demonstrated an immediate elevation of the proinflammatory cytokines IL-1 beta and IL-6 in their plasma. These cytokine levels appeared to peak after 1-2 weeks of xRT Wore returning toward pre xRT levels. In contrast, the profibrotic cytokine TGF beta appeared to decrease immediately following initiation of xRT but, subsequently, underwent two distinct waves of elevation, occurring at 1-2 weeks and 5-6 weeks into the xRT. Surprisingly, while the temporal pattern of plasma cytokine response was similar in both treatment groups, the magnitude of cytokine expression was noticeably different, appearing to be significantly affected by the addition of TAS. Indeed, administration of neoadjuvant TAS appeared to bring about a marked elevation of IL-1 beta and IL-6 and a significant reduction in TGF beta when compared to patients receiving xRT alone. Conclusion: The precise mechanisms underlying this TAS-related increase of the proinflaminatory cytokines IL-1 and IL-6 and decrease of the profibrotic cytokine TGF beta remain unclear, However, previous reports have documented that androgens tend to be immunosuppressive in nature. It is conceivable, therefore, that administration of TAS shifts the ratio of pro inflammatory and profibrotic cytokines toward a more immunostimulatory state.