title: Interleukin-1 as a mediator of fatigue in disease: a narrative review.
abstract: Fatigue is commonly reported in a variety of illnesses, and it has major impact on quality of life. Previously, it was thought that fatigue originates in the skeletal muscles, leading to cessation of activity. However, more recently, it has become clear that the brain is the central regulator of fatigue perception. It has been suggested that pro-inflammatory cytokines, especially interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β), play a prominent role in the development of central fatigue, and several studies have been performed to elucidate the connection between inflammation and these central processes.In this narrative review, mechanisms of action of IL-1 are described, with special attention to its effect on the central nervous system. In addition, we present a summary of studies that (i) investigated the relationship between circulating IL-1α and IL-1β and fatigue severity and/or (ii) evaluated the effect of inhibiting IL-1 on fatigue. We aim to improve the understanding of fatigue in both inflammatory and non-inflammatory illnesses, which could help develop strategies to treat fatigue more effectively.Reviewing the studies that have been performed, it appears that there is a limited value of measuring circulating IL-1. However, inhibiting IL-1 has a positive effect on severe fatigue in most studies that have been conducted.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6500HB, Nijmegen, The Netherlands. Megan.Roerink@radboudumc.nl.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Roerink
authors.affiliation: Expert Centre for Chronic Fatigue, Radboud University Medical Centre, Reinier Postlaan 4, 6525GC, Nijmegen, The Netherlands.
authors.forename: Marieke E
authors.initials: ME
authors.lastname: van der Schaaf
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6500HB, Nijmegen, The Netherlands.|Department of Medicine, University of Colorado Denver, 12700 E. 19th Avenue Box B168, Aurora, CO, 80045, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Expert Centre for Chronic Fatigue, Radboud University Medical Centre, Reinier Postlaan 4, 6525GC, Nijmegen, The Netherlands.|Department of Medical Psychology, Academic Medical Centre (AMC), University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Knoop
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6500HB, Nijmegen, The Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005221:Fatigue / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*
chemical_list: D007375:Interleukin-1
keywords: Fatigue; Inhibition; Interleukin 1; Treatment