Altered immune pathway activity under exercise challenge in Gulf War Illness: An exploratory analysis

Gordon Broderick, Rotem Ben-Hamo, Saurabh Vashishtha, Sol Efroni, Lubov Nathanson, Zachary Barnes, Mary Ann Fletcher, Nancy Klimas

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating illness presenting with a complex constellation of immune, endocrine and neurological symptoms. Here we compared male GWI (n= 20) with healthy veterans (n= 22) and subjects with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) (n= 7). Blood was drawn during a Graded eXercise Test (GXT) prior to exercise, at peak effort (VO2 max) and 4-h post exercise. Affymetrix HG U133 plus 2.0 microarray gene expression profiling in peripheral blood mononuclear cells (PBMCs) was used to estimate activation of over 500 documented pathways. This was cast against ELISA-based measurement of 16 cytokines in plasma and flow cytometric assessment of lymphocyte populations and cytotoxicity. A 2-way ANOVA corrected for multiple comparisons (q statistic <0.05) indicated significant increases in neuroendocrine-immune signaling and inflammatory activity in GWI, with decreased apoptotic signaling. Conversely, cell cycle progression and immune signaling were broadly subdued in CFS. Partial correlation networks linking pathways with symptom severity via changes in immune cell abundance, function and signaling were constructed. Central to these were changes in IL-10 and CD2+ cell abundance and their link to two pathway clusters. The first consisted of pathways supporting neuronal development and migration whereas the second was related to androgen-mediated activation of NF-κB. These exploratory results suggest an over-expression of known exercise response mechanisms as well as illness-specific changes that may involve an overlapping stress-potentiated neuro-inflammatory response.

Original languageEnglish
Pages (from-to)159-169
Number of pages11
JournalBrain, Behavior, and Immunity
Volume28
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Fingerprint

Gulf War
Chronic Fatigue Syndrome
Exercise
Gene Expression Profiling
Veterans
Antigen-Antibody Complex
Exercise Test
Interleukin-10
Androgens
Blood Cells
Analysis of Variance
Cell Cycle
Enzyme-Linked Immunosorbent Assay
Lymphocytes
Cytokines
Population

Keywords

  • Exercise challenge
  • Gene expression
  • Gulf War Illness
  • Mathematical immunology
  • Pathway activity

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Broderick, G., Ben-Hamo, R., Vashishtha, S., Efroni, S., Nathanson, L., Barnes, Z., ... Klimas, N. (2013). Altered immune pathway activity under exercise challenge in Gulf War Illness: An exploratory analysis. Brain, Behavior, and Immunity, 28, 159-169. https://doi.org/10.1016/j.bbi.2012.11.007

Altered immune pathway activity under exercise challenge in Gulf War Illness : An exploratory analysis. / Broderick, Gordon; Ben-Hamo, Rotem; Vashishtha, Saurabh; Efroni, Sol; Nathanson, Lubov; Barnes, Zachary; Fletcher, Mary Ann; Klimas, Nancy.

In: Brain, Behavior, and Immunity, Vol. 28, 01.02.2013, p. 159-169.

Research output: Contribution to journalArticle

Broderick, G, Ben-Hamo, R, Vashishtha, S, Efroni, S, Nathanson, L, Barnes, Z, Fletcher, MA & Klimas, N 2013, 'Altered immune pathway activity under exercise challenge in Gulf War Illness: An exploratory analysis', Brain, Behavior, and Immunity, vol. 28, pp. 159-169. https://doi.org/10.1016/j.bbi.2012.11.007
Broderick, Gordon ; Ben-Hamo, Rotem ; Vashishtha, Saurabh ; Efroni, Sol ; Nathanson, Lubov ; Barnes, Zachary ; Fletcher, Mary Ann ; Klimas, Nancy. / Altered immune pathway activity under exercise challenge in Gulf War Illness : An exploratory analysis. In: Brain, Behavior, and Immunity. 2013 ; Vol. 28. pp. 159-169.
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