Research Article Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome Megan Lynn , 1 Laura Maclachlan, 2 Andreas Finkelmeyer, 1 James Clark, 1 James Locke, 3 Stephen Todryk, 3,4 Wan-Fai Ng, 3,5 Julia L. Newton, 3,5 and Stuart Watson 1,6 1 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK 2 Department of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden 3 Institute of Cellular Medicine and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK 4 Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK 5 Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK 6 Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK Correspondence should be addressed to Stuart Watson; stuart.watson@ncl.ac.uk Received 11 January 2018; Revised 20 April 2018; Accepted 7 May 2018; Published 10 June 2018 Academic Editor: Ronald Gladue Copyright © 2018 Megan Lynn et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glucocorticoid receptor (GR) function may have aetiopathogenic significance in chronic fatigue syndrome (CFS), via its essential role in mediating inflammatory responses as well as in hypothalamic-pituitary-adrenal axis regulation. GR function can be estimated ex vivo by measuring dexamethasone (dex) modulation of cytokine response to lipopolysaccharide (LPS), and in vivo using the impact of dex on cortisol levels. This study aimed to compare the GR function between CFS (n = 48), primary Sjögren’s syndrome (a disease group control) (n = 27), and sedentary healthy controls (HCs) (n = 20), and to investigate its relationship with clinical measures. In the GR ex vivo response assay, whole blood was diluted and incubated with LPS (to stimulate cytokine production), with or without 10 or 100 nanomolar concentrations of dex. Cytometric bead array (CBA) and flow cytometry enabled quantification of cytokine levels (TNFα, interleukin- (IL-) 6, and IL-10) in the supernatants. In the in vivo response assay, five plasma samples were taken for determination of total cortisol concentration using ELISA at half-hourly intervals on two consecutive mornings separated by ingestion of 0.5 mg of dex at 11 pm. The association of the data from the in vivo and ex vivo analyses with reported childhood adversity was also examined. CFS patients had reduced LPS-induced IL-6 and TNFα production compared to both control groups and reduced suppression of TNFα by the higher dose of dex compared to HCs. Cortisol levels, before or after dex, did not differ between CFS and HCs. Cortisol levels were more variable in CFS than HCs. In the combined group (CFS plus HC), cortisol concentrations positively and ex vivo GR function (determined by dex-mediated suppression of IL-10) negatively correlated with childhood adversity score. The results do not support the hypothesis that GR dysregulation is aetiopathogenic in CFS and suggest that current and future endocrine cross-sectional studies in CFS may be vulnerable to the confounding influence of childhood trauma which is likely increased by comorbid depression. 1. Introduction Chronic fatigue syndrome (CFS) has a prevalence of 2% in the UK [1, 2]. It is defined by profound, persistent, medically unexplained fatigue lasting at least 6 months, which is not caused by ongoing exertion, not significantly eased by rest, and is severe enough to cause considerable loss of function [3–5]. Alongside this are symptoms of inflammation, pain, cognitive deficits, and psychiatric and bowel problems [4]. Often, biological tests and physical examinations are unre- markable. CFS affects all ages and the peak age of onset is 20–40. Full recovery is rare [2, 6] and comorbidity with depression is common. Many putative causes of CFS have been investigated but the absence of an agreed pathogenesis impacts the development of effective diagnostics and treatments. It is Hindawi Mediators of Inflammation Volume 2018, Article ID 3972104, 11 pages https://doi.org/10.1155/2018/3972104