СИНДРОМ ХРОНІЧНОЇ ВТОМИ: ВЗАЄМОЗВ'ЯЗОК ВПРАВ ТА ІМУННОЇ ДИСФУНКЦІЇ
CHRONIC FATIGUE SYNDROME: EXERCISE PERFORMANCE RELATED TO IMMUNE DYSFUNCTION
Jo Nijs1, 2, Mira Meeus1, 2, Neil R. Mcgregor3, Romain Meeusen1, Guy De Schutter1, Elke Van Hoof1, And Kenny De Meirleir1
'Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brüssel, Brussels, BELGIUM;
2Division of Musculoskeletal Physiotherapy, Department of Health Sciences, Hogeschool Antwerpen, Antwerp, BELGIUM; and
3Bio21, Institute- of Biomedical Research, University of Melbourne, Parksville, Victoria, AUSTRALIA
Анотація. Джо Нійс, Міра Меус і ін. Синдром хронічної втоми: взаємозв'язок вправ та імунної дисфункції. У статті наводяться дослідження взаємозв'язку фізичних вправ з внутрішньоклітинною імунною дисфункцією при синдромі хронічної втоми.
Ключові слова: фізичні вправи, імунітет, еластаза, протеїнкіназа R.
Аннотация. Джо Нийс, Мира Меус и др. Синдром хронической усталости: взаимосвязь упражнений и иммунной дисфункции. В статье описываются исследования взаимосвязи физических упражнений с внутриклеточной иммунной дисфункцией при синдроме хронической усталости.
Ключевые слова: физические упражнения, иммунитет, эластаза, протеинкиназа R.
Abstract. Jo Nijs, Mira Meeus ets. To date, the exact cause of abnormal exercise response in chronic fatigue syndrome (CFS) remains to be revealed, but evidence addressing intracellular immune deregulation in CFS is growing. Therefore, the aim of this cross-sectional study was to examine the interactions between several intracellular immune variables and exercise performance in CFS patients. Methods: After venous blood sampling, subjects (16 CFS patients) performed a maximal exercise stress test on a bicycle ergometer with continuous monitoring of cardiorespiratory variables. The following immune variables were assessed: the ratio of 37 kDa Ribonuclease (RNase) L to the 83 kDa native RNase L (using a radiolabeled ligand/receptor assay), RNase L enzymatic activity (enzymatic assay), protein kinase R activity assay (comparison Western blot), elastase activity (enzymatic-colorimetric assay), the percent of monocytes, and nitric oxide determination (for monocytes and lymphocytes; flow cytometry, live cell assay). Results: Forward stepwise multiple regression analysis revealed 1) that elastase activity was the only factor related to the reduction in oxygen uptake at a respiratory exchange ratio (RER) of 1. 0 (regression model: R2 = 0. 53, F (1, 14) = 15. 5, P < 0. 002; elastase activity P < 0. 002) ; 2) that the protein kinase R activity was the principle factor related to the reduction in workload at RER = 1. 0; and 3) that elastase activity was the principle factor related to the reduction in percent of target heart rate achieved. Conclusion: These data provide evidence for an association between intracellular immune deregulation and exercise performance in patients with CFS. To establish a causal relationship, further study of these interactions using a prospective longitudinal design is required.
Key words: exercise physiology, immunity, elastase, protein kinase R.
Previous research has shown that patients with chronic fatigue syndrome (CFS) present with an abnormal exercise response and exacerbation of symptoms after physical activity. Some of the main findings were a reduction in peak oxygen uptake (2, 10), reduction in peak heart rate (10), earlier exhaustion (10), and accelerated glycolysis with increased lactate production (30). Contrary to these findings, others found that the aerobic capacity of CFS patients lies within the low normal range (23). The highly heterogeneous nature of the CFS population and the lack of uniformity in both the utilized diagnostic criteria and exercise testing protocols preclude pooling of data and hence to draw firm conclusions. Still, we conclude that at least a subgroup of CFS patients present with an abnormal response to exercise. In addition, because several exercise capacity variables (e. g., functional aerobic impairment, body weight-adjusted peak oxygen uptake, exercise duration) correlated with activity limitations/participation restrictions (20), evidence supporting the clinical importance of impairments in exercise performance fitness in CFS patients was provided (i. e., a poor exercise performance was associated with more severe activity limitations/participation restrictions). Importantly, the exacerbation of symptoms after exercise is seen only in the CFS population, and not in fatigue-associated disorders such as depression, rheumatoid arthritis, systemic lupus erythematosus, or multiple sclerosis (26). To date, the exact cause of the abnormal exercise performance in CFS remains to be elucidated. Earlier attempts revealed that in CFS patients kinesiophobia (irrational fear of movement) is not related to exercise performance (18), and that an exercise challenge further enhances complement activation (26).
Type I interferons trigger the 2', 5'-oligoadenylate (2-5A) synthetase/Ribonuclease (RNase) L activation and induce the expression of the double-stranded RNA dependent protein kinase R (PKR). The PKR enzyme and 2-5A syn-thetase/RNase L system are termed the «cellular double-stranded RNA-detecting systems» that are responsible for the translational inhibition in response to (viral) infection (11). The deregulation of the 2-5A synthetase/RNase L pathway in subsets of CFS patients has been reported at length in the scientific literature (3, 27, 28). Both elastases and calpain are capable