Plasma cytokine expression in adolescent chronic fatigue syndrome Vegard Bruun Wyllera, b, c, , , Øystein Sørensend, Dag Sulheima, e, Even Fagermoenf, g, Thor Uelandh, i, Tom Eirik Mollnesj, k, l Highlights • Chronic fatigue syndrome (CFS) might be related to altered cytokine expression. • A total of 120 adolescent CFS patients and 68 healthy controls were studied. • Individual cytokine levels where similar across the two groups. • Cytokine network parameters (ARACNE algorithm) were similar across the two groups. • In CFS patients, there were no associations between symptoms and network parameters. Abstract Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12–18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p < 0.001) and inflammatory symptoms (p < 0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and there were no associations between symptoms and cytokine expression in the CFS group. Low-grade systemic inflammation does not appear to be a central part of adolescent CFS pathophysiology. Keywords Chronic fatigue syndrome; Adolescent; Inflammation; Cytokine Corresponding author at: Dept. of Paediatrics, Akershus University Hospital, N-1478 Lørenskog, Norway. Tel.: +47 91 16 66 81. Copyright © 2014 Published by Elsevier Inc . http://www.sciencedirect.com/science/article/pii/S088915911400614X In this study Wyller is applying a unique (to him?) definition - broader than Fukuda, more like Oxford with 3 months of fatigue as the only symptom required.