A formal analysis of cytokine networks in Chronic Fatigue Syndrome

Gordon Broderick, Jim Fuite, Andrea Kreitz, Suzanne D. Vernon, Nancy Klimas, Mary Ann Fletcher

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Chronic Fatigue Syndrome (CFS) is a complex illness affecting 4 million Americans for which no characteristic lesion has been identified. Instead of searching for a deficiency in any single marker, we propose that CFS is associated with a profound imbalance in the regulation of immune function forcing a departure from standard pre-programmed responses. To identify these imbalances we apply network analysis to the co-expression of 16 cytokines in CFS subjects and healthy controls. Concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12, 13, 15, 17 and 23, IFN-γ, lymphotoxin-α (LT-α) and TNF-α were measured in the plasma of 40 female CFS and 59 case-matched controls. Cytokine co-expression networks were constructed from the pair-wise mutual information (MI) patterns found within each subject group. These networks differed in topology significantly more than expected by chance with the CFS network being more hub-like in design. Analysis of local modularity isolated statistically distinct cytokine communities recognizable as pre-programmed immune functional components. These showed highly attenuated Th1 and Th17 immune responses in CFS. High Th2 marker expression but weak interaction patterns pointed to an established Th2 inflammatory milieu. Similarly, altered associations in CFS provided indirect evidence of diminished NK cell responsiveness to IL-12 and LT-α stimulus. These observations are consistent with several processes active in latent viral infection and would not have been uncovered by assessing marker expression alone. Furthermore this analysis identifies key sub-networks such as IL-2:IFN-γ:TNF-α that might be targeted in restoring normal immune function.

Original languageEnglish
Pages (from-to)1209-1217
Number of pages9
JournalBrain, Behavior, and Immunity
Volume24
Issue number7
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Chronic Fatigue Syndrome
Cytokines
Lymphotoxin-alpha
Virus Diseases
Interleukin-12
Natural Killer Cells
Interleukin-2
Healthy Volunteers

Keywords

  • Chronic fatigue
  • Cytokines
  • Immune signaling
  • Inflammation
  • Latent viral infection
  • Network theory

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Broderick, G., Fuite, J., Kreitz, A., Vernon, S. D., Klimas, N., & Fletcher, M. A. (2010). A formal analysis of cytokine networks in Chronic Fatigue Syndrome. Brain, Behavior, and Immunity, 24(7), 1209-1217. https://doi.org/10.1016/j.bbi.2010.04.012

A formal analysis of cytokine networks in Chronic Fatigue Syndrome. / Broderick, Gordon; Fuite, Jim; Kreitz, Andrea; Vernon, Suzanne D.; Klimas, Nancy; Fletcher, Mary Ann.

In: Brain, Behavior, and Immunity, Vol. 24, No. 7, 01.10.2010, p. 1209-1217.

Research output: Contribution to journalArticle

Broderick, G, Fuite, J, Kreitz, A, Vernon, SD, Klimas, N & Fletcher, MA 2010, 'A formal analysis of cytokine networks in Chronic Fatigue Syndrome', Brain, Behavior, and Immunity, vol. 24, no. 7, pp. 1209-1217. https://doi.org/10.1016/j.bbi.2010.04.012
Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA. A formal analysis of cytokine networks in Chronic Fatigue Syndrome. Brain, Behavior, and Immunity. 2010 Oct 1;24(7):1209-1217. https://doi.org/10.1016/j.bbi.2010.04.012
Broderick, Gordon ; Fuite, Jim ; Kreitz, Andrea ; Vernon, Suzanne D. ; Klimas, Nancy ; Fletcher, Mary Ann. / A formal analysis of cytokine networks in Chronic Fatigue Syndrome. In: Brain, Behavior, and Immunity. 2010 ; Vol. 24, No. 7. pp. 1209-1217.
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