Cytokine dysregulation and cancer-related fatigue in exercise

Fatigue is the most frequent and severe symptom accompanying cancer and its treatment and has a significant effect on patient's functional status and quality of life. Despite this, the pathophysiological mechanisms involved in cancer-related fatigue (CRF) are yet to be fully determined. The cytokine dysregulation hypothesis has been implicated by many experts in the pathogenesis of CRF and may account for many of the symptoms accompanying cancer and its treatment. However, the relationship between cytokine dysregulation and CRF is not well established. One approach to enhance our understanding of the pathophysiological mechanisms involved in CRF may be to examine exercise-induced fatigue in cancer patients using electrophysiological and neurobiological techniques. Studies using this approach to investigate CRF are scarce, but available results demonstrate a greater contribution from central processes to the development of physical fatigue in cancer patients compared with healthy controls. Interestingly, evidence exists to suggest that cytokine dysregulation associated with cancer and its treatment may induce central fatigue through a number of different mechanisms; specifically, altered serotonin metabolism, hypothalamic-pituitary-adrenal axis dysfunction, and vagal afferent nerve activation. However, further research examining the contribution of these mechanisms are needed before any conclusions can be drawn. The results from such studies may provide new insights into the pathophysiological mechanisms involved in CRF and assist in the development of successful interventions to reduce the physiological fatigue burden in cancer patients and their carers.