Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

Abstract

Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development. A description of the features of central fatigue is provided, and the current evidence describing the association between inflammation and fatigue in various medical conditions is reviewed. Additionally, the effect of inflammation on specific neuronal processes that may be involved in distinct fatigue dimensions is described. We suggest that the multidimensional aspects of fatigue should be assessed in future studies of inflammation-induced fatigue and that this would benefit the development of effective therapeutic interventions.

Systemic inflammation and immune cell phenotypes are associated with neuro‐psychiatric symptoms in patients with chronic inflammatory liver diseases

“…Various cytokines and chemokines are produced during chronic inflammatory liver diseases at the site of infection which can contribute to protection against pathogens but may also be involved in pathology . Alterations in inflammatory mediators are also found in the blood and are therefore capable of acting systematically on distant organs like the brain . Here, we show in a comprehensive analysis of patients with various inflammatory liver diseases that (i) soluble inflammatory mediators are up‐regulated and (ii) NK‐ and T‐ cells are less activated in patients with neuropsychiatric symptoms compared to patients without these symptoms.…”

“…Currently two variants of “immune‐to‐brain‐pathways” are particularly discussed: the neuronal pathway via the vagus nerve and the humoral pathway which comprises passage of inflammatory cytokines and chemokines across the blood‐brain‐barrier (BBB) or after disease‐related alterations of the BBB . Within the brain the immune modulators not only interfere with neurotransmission and neuroendocrine systems but also stimulate cerebral production of cytokines by endothelial and glial cells – finally resulting in various neuropsychiatric symptoms.…”

The role of neuro‐immune interactions in cancer‐related fatigue: Biobehavioral risk factors and mechanisms

“…Very few neuroimaging studies in patients with cancer have examined links with fatigue, focusing instead on cognitive function. However, there is growing interest in the neural processes that underlie fatigue in the context of cancer and other medical conditions, with conceptual models focusing on the anterior insula and frontostriatal network as key pathways involved in fatigue . This work builds on research examining the inflammatory mechanisms that underlie depression, which has highlighted a role for the dopamine system in fatigue and other neurovegetative symptoms …”

“…However, there is growing interest in the neural processes that underlie fatigue in the context of cancer and other medical conditions, with conceptual models focusing on the anterior insula and frontostriatal network as key pathways involved in fatigue. 110,111 This work builds on research examining the inflammatory mechanisms that underlie depression, which has highlighted a role for the dopamine system in fatigue and other neurovegetative symptoms. 112 A few studies have examined neural processes related to fatigue in patients with cancer and survivors, although methods and processes vary across reports.…”

Acceptance & Commitment Therapy for ME/CFS (Chronic Fatigue Syndrome) – A feasibility study

“…The inherent mind-bodydualism perspective is an evident problem. Importantly, the developments within the field of psychoneuroimmunology makes debate regarding the mind or the body as the "cause" of symptoms and disability obsolete, with a growing body of research showing that psychological factors, stress, inflammation, the brain and behavior affect each other in complex ways (91). More so, the importance of psychological factors for how the illness affects functioning and quality of life is presumably as important as in other longstanding somatic conditions (92)(93)(94)(95)(96)(97).…”