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.


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)-1beta, 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-1beta 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 TGFbeta 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-1beta and IL-6 and a significant reduction in TGFbeta when compared to patients receiving xRT alone.


CONCLUSIONS
The precise mechanisms underlying this TAS-related increase of the proinflammatory cytokines IL-1beta and IL-6 and decrease of the profibrotic cytokine TGFbeta 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.
Johnke
Roberta M
RM
Department of Radiation Oncology, East Carolina University Brody School of Medicine, Greenville, North Carolina, USA. tracyr@ecu.edu
Edwards
Judy M
JM
Evans
Mark J
MJ
Nangami
Gladys N
GN
Bakken
Nicholas T G
NT
Kilburn
Jeremy M
JM
Lee
Tung-Kwang
TK
Allison
Ron R
RR
Karlsson
Ulf L
UL
Arastu
Hyder H
HH
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000628:therapy; D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D016207:Cytokines / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy; D018714:Radiotherapy, Adjuvant
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D016207:Cytokines