Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications

Abstract

Fatigue is one of the most common and distressing side effects of cancer and its treatment, and may persist for years after treatment completion in otherwise healthy survivors. Guided by basic research on neuro-immune interactions, a growing body of research has examined the hypothesis that cancer-related fatigue is driven by activation of the pro-inflammatory cytokine network. In this review, we examine the current state of the evidence linking inflammation and cancer-related fatigue, drawing from recent human research and from experimental animal models probing effects of cancer and cancer treatment on inflammation and fatigue. In addition, we consider two key questions that are currently driving research in this area: what are the neural mechanisms of fatigue, and what are the biological and psychological factors that influence the onset and/or persistence of inflammation and fatigue in cancer patients and survivors? Identification of the mechanisms driving cancer-related fatigue and associated risk factors will facilitate the development of targeted interventions for vulnerable patients.

Figure 1

Conceptual model linking cancer and cancer treatments to inflammation and symptoms of fatigue. These effects may be mediated by alterations in dopaminergic transmission; the dashed line around this mediator indicates that this pathway has not been fully elucidated. Host factors that may influence that onset and persistence of inflammation and fatigue in cancer patients are depicted in circles and include genetic polymorphisms, alterations in the hypothalamic-pituitary-adrenal (HPA) axis, alterations in the cellular immune system, and biobehavioral factors such as history of depression, sleep disturbance, early life stress, and body mass index.