Abstract
Fatigue is a term that describes exhaustion as either physically measurable, usually muscular, or perceived. Fatigue as a condition is observed in a wide range of long-term stresses such as chronic infectious, autoimmune, or oncologic diseases as well as mental disorders. This article provides an overview of the currently known biopsychosocial interactions between fatigue, psychosocial stress, and immune response. It describes how chronic inflammatory processes and stress interact in fatigue and for which therapeutic approaches there is evidence to date.Given the current psychoneuroimmunological knowledge and the biopsychosocial model, both high physical and psychosocial stress can converge in neuroendocrine-immunological dysregulation. According to this model, symptoms of fatigue correspond to a chronically overactivated innate immune response. At the same time, chronic immune activation favors a misactivation of the learned immune response, which is dominated by (auto)antibody production and hyperactivated T lymphocytes. However, patients who report fatigue do not necessarily display immunological dysregulations. There is currently a need for research and education in order to identify patient subpopulations and specifically tailored treatment concepts to them.