Fatigue Research Today is a free monthly online journal that collates and summarizes the latest research about Fatigue, including details on chronic fatigue syndrome, exhaustion, causes, diagnosis.

Inflammatory biomarkers for persistent fatigue in breast cancer survivors.

Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR

Cousins Center for Psychoneuroimmunology, University of California at Los Angeles Semel Institute for Neuroscience and Human Behavior, Los Angeles, California 90095-7076, USA.

PURPOSE: This study seeks to define immunologic and inflammatory variables associated with persistent post-treatment fatigue in breast cancer survivors. EXPERIMENTAL DESIGN: Leukocyte subsets, plasma inflammatory markers, and ex vivo proinflammatory cytokine production were assessed in 50 fatigued and nonfatigued breast cancer survivors recruited > or = 2 years after successful primary therapy. Multivariate statistical analyses were used to define a composite immunologic biomarker of fatigue risk. RESULTS: Fatigued breast cancer survivors were distinguished from nonfatigued survivors by increased ex vivo monocyte production of interleukin (IL)-6 and tumor necrosis factor-alpha following lipopolysaccharide stimulation, elevated plasma IL-1ra and soluble IL-6 receptor (sIL-6R/CD126), decreased monocyte cell-surface IL-6R, and decreased frequencies of activated T lymphocytes and myeloid dendritic cells in peripheral blood (all P < 0.05). An inverse correlation between sIL-6R and cell-surface IL-6R was consistent with inflammation-mediated shedding of IL-6R, and in vitro studies confirmed that proinflammatory cytokines induced such shedding. Multivariate linear discriminant function analysis identified two immunologic markers, the ratio of sIL-6R to monocyte-associated IL-6R and decreased circulating CD69+ T lymphocytes, as highly diagnostic of fatigue (P = 0.0005), with cross-validation estimates indicating 87% classification accuracy (sensitivity = 0.83; specificity = 0.83). CONCLUSION: These results extend links between fatigue and inflammatory markers to show a functional alteration in proinflammatory cytokine response to lipopolysaccharide and define a prognostic biomarker of behavioral fatigue.

Published 5 May 2006 in Clin Cancer Res, 12(9): 2759-66.
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