Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.
OBJECTIVE
Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) are characterized by debilitating fatigue, yet evaluation of this symptom is subjective. We examined metabolite-detecting, adrenergic, and immune gene expression (messenger ribonucleic acid [mRNA]) in patients with CFS (n = 22) versus patients with MS (n = 20) versus healthy controls (n = 23) and determined their relationship to fatigue and pain before and after exercise.


METHODS
Blood samples and fatigue and pain ratings were obtained at baseline and 0.5, 8, 24, and 48 hours after sustained moderate exercise. Leukocyte mRNA of four metabolite-detecting receptors (acid-sensing ion channel 3, purinergic type 2X4 and 2X5 receptors, and transient receptor potential vanilloid type 1) and four adrenergic (α-2a, β-1, and β-2 receptors and catechol-O-methyltransferase) and five immune markers (CD14, toll-like receptor 4 [TLR4], interleukin [IL] 6, IL-10, and lymphotoxin α) was examined using quantitative polymerase chain reaction.


RESULTS
Patients with CFS had greater postexercise increases in fatigue and pain (10-29 points above baseline, p < .001) and greater mRNA increases in purinergic type 2X4 receptor, transient receptor potential vanilloid type 1, CD14, and all adrenergic receptors than controls (mean ± standard error = 1.3 ± 0.14- to 3.4 ± 0.90-fold increase above baseline, p = .04-.005). Patients with CFS with comorbid fibromyalgia (n = 18) also showed greater increases in acid-sensing ion channel 3 and purinergic type 2X5 receptors (p < .05). Patients with MS had greater postexercise increases than controls in β-1 and β-2 adrenergic receptor expressions (1.4 ± 0.27- and 1.3 ± 0.06-fold increases, respectively, p = .02 and p < .001) and greater decreases in TLR4 (p = .02). In MS, IL-10 and TLR4 decreases correlated with higher fatigue scores.


CONCLUSIONS
Postexercise mRNA increases in metabolite-detecting receptors were unique to patients with CFS, whereas both patients with MS and patients with CFS showed abnormal increases in adrenergic receptors. Among patients with MS, greater fatigue was correlated with blunted immune marker expression.
Department of Anesthesiology, University of Utah, 30 N 1900 E, Room 3C444, Salt Lake City, UT 84132-2501, USA.
Andrea T
AT
White
Alan R
AR
Light
Ronald W
RW
Hughen
Timothy A
TA
Vanhaitsma
Kathleen C
KC
Light
D018663:Adrenergic Agents / Q000378:metabolism; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology; D005221:Fatigue / Q000235:genetics / Q000503:physiopathology; D015673:Fatigue Syndrome, Chronic / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005356:Fibromyalgia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D010146:Pain / Q000235:genetics / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism; D011983:Receptors, Purinergic / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D050916:TRPV Cation Channels; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D018663:Adrenergic Agents; D015415:Biomarkers; D007473:Ion Channels; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D011983:Receptors, Purinergic; D050916:TRPV Cation Channels; D051197:Toll-Like Receptor 4; D016753:Interleukin-10