Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome.
ABSTRACT Levels of 2',5'-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls. Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6). Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.
- SourceAvailable from: Garth NicolsonClinical and Scientific Aspects of Myalgic Encepthalopathy/Chronic Fatigue Syndrome: The Practitioners Challenge, 06/2002: pages 179-181; Alison Hunter Foundation, Sydney, Australia.
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ABSTRACT: The aim of this study was to measure the activity of 2',5'-oligoadenylate synthetase (2',5'AS) which is mainly induced by interferon (IFN)-α and -β in patients with major depression and evaluate its relationship to the disease. 2',5'AS activity of 23 patients (male = 11, female = 12) with major depression and of 29 normal control subjects (male = 15, female = 14) was measured in peripheral blood mononuclear cells (PBMCs) by radioassay. The mean 2',5'AS activity in the PBMCs of the patients and that of the control subjects were 1.10 ± 0.69% and 0.72 ± 0.51%, respectively. The activity in the patients was statistically higher than that of the control subjects ( P = 0.03). These results imply some abnormality in the IFN-2',5'AS system of patients with major depression.
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ABSTRACT: An increasing number of studies have examined how the immune system of patients with Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis, responds to exercise. The objective of the present study was to systematically review the scientific literature addressing exercise-induced immunological changes in CFS patients compared to healthy control subjects. A systematic literature search was conducted in the PubMed and Web of science databases using different keyword combinations. We included 23 case control studies that examined whether CFS patients, compared to healthy sedentary controls, have a different immune response to exercise. The included articles were evaluated on their methodological quality. Compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells' gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines. Many of these immune changes relate to post-exertional malaise in CFS, a major characteristic of the illness. The literature review provides level B evidence for an altered immune response to exercise in patients with CFS.Exercise immunology review 01/2014; 20:94-116. · 9.93 Impact Factor