Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness

• Published in: Brain, behavior, & immunity. Health Vol. 29; p. 100612
• Main Authors: Boruch, Alexander E., Lindheimer, Jacob B., Ninneman, Jacob V., Wylie, Glenn R., Alexander, Thomas, Klein-Adams, Jacquelyn C., Stegner, Aaron J., Gretzon, Nicholas P., Samy, Bishoy, Falvo, Michael J., Cook, Dane B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2023; Elsevier
• Subjects: Exercise test; Full Length; Gulf war; Mediation analysis; MeSH terms: Gene expression; Symptom flare up; Veterans health; MeSH terms: Gene expression; Veterans health; Exercise test; Gulf war; Symptom flare up; Mediation analysis
• ISSN: 2666-3546; 2666-3546
• DOI: 10.1016/j.bbih.2023.100612

Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. To investigate whether PEM is meditated by gene expression in Veterans with GWI. Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n = 25) provided blood samples before and after 30-min of cycling at 70% of age-predicted heart rate reserve. Relative quantification of gene expression, symptom measurements, and select cardiopulmonary parameters were compared between groups at pre-, 30 minpost-, and 24 hpost-exercise using a doubly multivariate repeated measures analysis of variance (RM-MANOVA). Mediation analyses were used to test indirect effects of changes in gene expression on symptom responses (i.e., PEM) to the standardized exercise challenge. Veterans with GWI experienced large symptom exacerbations following exercise compared to controls (Cohen's d: 1.65; p < 0.05). Expression of β-actin (ACTB), catechol-O-methyltransferase (COMT), and toll-like receptor 4 (TLR4) decreased in Veterans with GWI at 30 min (p < 0.05) and 24 h post-exercise (p < 0.05). Changes in gene expression did not mediate post-exercise symptom exacerbation in GWI (Indirect Effect Slope Coefficient: 0.06 – 0.02; 95% CI: 0.19, 0.12). An acute bout of moderate intensity cycling reduced the expression of select structural, adrenergic, and immune genes in Veterans with GWI, but the pathophysiological relevance to PEM is unclear. •Gulf War Veterans with GWI experience PEM.•GWI had significantly lower post-exercise ACTB, COMT, and TLR4 gene expression.•Gene expression did not mediate symptom post-exercise symptom exacerbation.•Post-exercise gene expression differs from responses reported in ME/CFS.•This suggests potentially unique GWI pathophysiology vs. previous ME/CFS reports.