TY - JOUR T1 - Circulating Cytokine Levels in Prostate Cancer Patients Undergoing Radiation Therapy: Influence of Neoadjuvant Total Androgen Suppression JF - In Vivo JO - In Vivo SP - 827 LP - 833 VL - 23 IS - 5 AU - ROBERTA M. JOHNKE AU - JUDY M. EDWARDS AU - MARK J. EVANS AU - GLADYS N. NANGAMI AU - NICHOLAS T. G. BAKKEN AU - JEREMY M. KILBURN AU - TUNG-KWANG LEE AU - RON R. ALLISON AU - ULF L. KARLSSON AU - HYDER H. ARASTU Y1 - 2009/09/01 UR - http://iv.iiarjournals.org/content/23/5/827.abstract N2 - 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)-1β, IL-6 and transforming growth factor (TGF)β using ELISA procedures. Results: Following initiation of xRT, both patient groups demonstrated an immediate elevation of the proinflammatory cytokines IL-1β and IL-6 in their plasma. These cytokine levels appeared to peak after 1-2 weeks of xRT before returning toward pre xRT levels. In contrast, the profibrotic cytokine TGFβ 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-1β and IL-6 and a significant reduction in TGFβ when compared to patients receiving xRT alone. Conclusion: The precise mechanisms underlying this TAS-related increase of the proinflammatory cytokines IL-1β and IL-6 and decrease of the profibrotic cytokine TGFβ 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 proinflammatory and profibrotic cytokines toward a more immunostimulatory state. ER -