Inflammatory Biomarkers and Fatigue during Radiation Therapy for Breast and Prostate Cancer

Department of Psychology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1563, USA.
Clinical Cancer Research (Impact Factor: 8.72). 09/2009; 15(17):5534-40. DOI: 10.1158/1078-0432.CCR-08-2584
Source: PubMed


Biomarkers of radiation-induced behavioral symptoms, such as fatigue, have not been identified. Studies linking inflammatory processes to fatigue in cancer survivors led us to test the hypothesis that activation of the proinflammatory cytokine network is associated with fatigue symptoms during radiation therapy for breast and prostate cancer.
Individuals with early-stage breast (n = 28) and prostate cancer (n = 20) completed questionnaires and provided blood samples for determination of serum levels of interleukin 1beta (IL-1beta) and IL-6 at assessments conducted before, during, and after a course of radiation therapy. Serum markers of proinflammatory cytokine activity, including IL-1 receptor antagonist and C-reactive protein, were examined in a subset of participants. Random coefficient models were used to evaluate the association between changes in cytokine levels and fatigue.
As expected, there was a significant increase in fatigue during radiation treatment. Changes in serum levels of inflammatory markers C-reactive protein and IL-1 receptor antagonist were positively associated with increases in fatigue symptoms (Ps < 0.05), although serum levels of IL-1beta and IL-6 were not associated with fatigue. These effects remained significant (Ps < 0.05) in analyses controlling for potential biobehavioral confounding factors, including age, body mass index, hormone therapy, depression, and sleep disturbance.
Results suggest that activation of the proinflammatory cytokine network and associated increases in downstream biomarkers of proinflammatory cytokine activity are associated with fatigue during radiation therapy for breast and prostate cancer.

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Available from: Najib Aziz, Mar 12, 2014
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    • "a ) , a marker of IL - 1b activity ( Arend et al . , 1998 ) ; and C reactive protein ( CRP ) , a marker of IL - 6 activity ( Dayer et al . , 2007 ) . All of these markers have been associated with cancer related fatigue in previous research ( Bower et al . , 2002 ; Collado - Hidalgo et al . , 2006 ; Orre et al . , 2009 ; Alexander et al . , 2009 ; Bower et al . , 2009 ) . In addition , we assessed IL - 6 based on earlier yoga trials showing effects on this cyto kine ( Pullen et al . , 2008 , 2010 ) . Plasma levels of IL - 1ra and sTNF - RII were determined by ELISA ( R&D Systems , Minneapolis , MN ) according to the manufacturer ' s protocols , with a lower limit of detection of 31 and 234 pg / ml , "
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    • "As noted above, a cytokine cascade is an established consequence of RT. The production of proinflammatory cytokines, particularly IL-1β, IL-6, and TNF-α, occurs not only in tissue, but in peripheral blood and increased levels of systemic proinflammatory cytokines which correlate with nonhaematological toxicities [121, 148–151] after RT, suggesting that the mediators of toxicities are not simply compartmentalised into the radiation field. Indeed, peripheral activated cells (such as B-lymphocytes [152], myeloid lineage cells [149], and monocytes [11]) have an increased transcription of inflammation-related genes, particularly those responsive to the proinflammatory NF-κB transcription control pathway. "
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    • "The association between fatigue and inflammatory cytokine release has been extensively researched in the clinical radiation therapy setting, often with conflicting outcomes. In a study by Bower et al. [41] of 28 breast cancer and prostate cancer patients receiving radiation therapy, clinical fatigue was significantly associated with CRP and IL-1, the downstream biomarkers of the pro-inflammatory cytokines IL-1b and IL-6, respectively. A similar study in breast cancer patients by Wratten et al. [91] showed Fig. 1. "
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