Cancer-related fatigue: links with inflammation in cancer patients and survivors

Abstract

Fatigue is one of the most common and distressing side effects of cancer and its treatment and may persist long after successful treatment completion. Emerging evidence suggests that inflammatory processes may be involved in cancer-related fatigue both during and after treatment. In this review, we consider the evidence for an association between inflammation and fatigue in cancer patients and survivors. Further, we identify potential mechanisms for persistent inflammation, focusing on the HPA axis. Risk factors and treatments for cancer-related fatigue are also discussed.

Figure 1

Potential mechanisms for cancer-related fatigue, focusing on factors identified or implicated by our research. Cancer and its treatment can activate the proinflammatory cytokine network, leading to symptoms of fatigue through cytokine effects on the central nervous system. Chronic inflammation may develop when cancer and cancer treatments induce long-term changes in immune homeostasis, including alterations in immune cell subsets, alterations in expression and signaling of Toll-like receptors, and latent virus reactivation. Cancer-related changes in neuroendocrine function may also contribute to chronic inflammation, particularly impairments in glucocorticoid production that result in ineffective control of inflammatory processes. In addition, individual difference factors may increase the risk for chronic inflammation following cancer diagnosis and treatment. Potential risk factors include single nucleotide polymorphisms in cytokine genes, alterations in HPA axis function, and depressive symptoms. Of note, HPA dysregulation and depression may also have direct effects on fatigue.