Research Abstract:
The role of IP-10 in Chronic Fatigue Syndrome, by Anne McArdle, Arief Gusnanto, Kate Ear, George Sakellariou, Clare Lawton, Daniel Owens, Graeme Close, Michael Beadsworth, Louise Dye in FASEB Journal Vol. 31:1 Supplement, lb789 April 2017
Chronic fatigue syndrome (CFS) is a severely debilitating and complex illness of uncertain cause, characterised by prolonged, fatigue triggered by minimal activity. There is evidence that CFS is associated with chronic inflammation. Studies have shown that plasma levels of cytokines are chronically modified in patients with CFS.
This study examined physiological, subjective and cognitive factors associated with plasma cytokine concentrations in a cohort of 92 patients compared with age and sex matched healthy controls. A sub-group of patients and healthy controls (HCs) also underwent more detailed analyses of muscle function, cytokine production and cognitive function.
Patients were diagnosed with CFS if they met the Oxford criteria for Chronic Fatigue Syndrome and recommended NICE guidelines. Patients completed a number of validated questionnaires including the Chalder Fatigue Questionnaire (CFQ) which is considered a valid and reliable measure of fatigue in patients with CFS.
Patients with CFS demonstrated a characteristic significant reduction in Maximal Voluntary Contraction Force compared with HCs. Data on plasma concentrations of 27 pro- and anti-inflammatory cytokines were analysed using multiple or logistic regression with age and sex which were significant covariates included in each model.
CFS was strongly associated with a limited number of cytokines. Diagnosis of CFS was associated with increased plasma contents of MIP-1a, MIP-1b and RANTES (p<0.05) and marginally with Eotaxin (p=0.07) when modelled individually. MVC and self-reported fatigue both showed particularly strong associations with plasma IP-10 concentrations. Muscle content of IP-10 mRNA was significantly elevated, suggesting that, at least in part, muscle was a source of this IP-10 but not the other cytokines.
Pairwise associations between MVC and cytokines demonstrated that the reduced MVC seen in patients with CFS was strongly associated with plasma levels of IP-10, TNF-alpha and IL-5. Further analyses revealed strong correlations between plasma RANTES and eotaxin levels and poorer verbal recall and RTs of patients with CFS. The consistent association of IP-10 with the physiological features and of RANTES and eotaxin with the cognitive features of CFS provides compelling evidence for a role of these cytokine/ chemokines in the physiological and cognitive pathology of CFS.
This work was funded by the Medical Research Council.
