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Open Access Highly Accessed Research

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

Elizabeth Ann Stringer1, Katharine Susanne Baker1, Ian R Carroll1, Jose G Montoya2, Lily Chu5, Holden T Maecker3 and Jarred W Younger14*

Author Affiliations

1 Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, 94304, USA

2 Department of Medicine, Infectious Diseases, Stanford University School of Medicine, Stanford, CA, 94304, USA

3 Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, 94304, USA

4 1070 Arastradero Road, Suite 200, Palo Alto, CA, 94304-1336, USA

5 Independent Consultant, Stanford, CA, 94304, USA

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Journal of Translational Medicine 2013, 11:93  doi:10.1186/1479-5876-11-93

Published: 9 April 2013

Abstract

Background

Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.

Methods

Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.

Results

Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.

Conclusions

Our results support the role of cytokines in the pathophysiology of CFS.

Keywords:
Chronic fatigue syndrome; Cytokines; Leptin; Daily immune monitoring