Pathogenesis Of Chronic Fatigue Syndrome Research Articles

Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine

Chronic Fatigue Syndrome (CFS) is a complex and perplexing medical disorder primarily characterized by persistent and debilitating fatigue, often accompanied by a constellation of symptoms, including weakness, dyspnea, arthromyalgia, sore throat, and disrupted sleep patterns. CFS is defined by its persistent or recurrent manifestation for a minimum duration of six months, marked by an enduring and unrelenting fatigue that remains refractory to rest. In recent decades, this condition has garnered significant attention within the medical community. While the precise etiology of CFS remains elusive, it is postulated to be multifactorial. CFS is potentially associated with various contributory factors such as infections, chronic stress, genetic predisposition, immune dysregulation, and psychosocial influences. The pathophysiological underpinnings of CFS encompass viral infections, immune system dysregulation, neuroendocrine aberrations, heightened oxidative stress, and perturbations in gut microbiota. Presently, clinical management predominantly relies on pharmaceutical interventions or singular therapeutic modalities, offering alleviation of specific symptoms but exhibiting inherent limitations. Traditional Chinese Medicine (TCM) interventions have emerged as a promising paradigm, demonstrating notable efficacy through their multimodal, multi-target, multi-pathway approach, and holistic regulatory mechanisms. These interventions effectively address the lacunae in contemporary medical interventions. This comprehensive review synthesizes recent advancements in the understanding of the etiological factors, pathophysiological mechanisms, and interventional strategies for CFS, drawing from a corpus of domestic and international literature. Its aim is to furnish valuable insights for clinicians actively involved in diagnosing and treating CFS, as well as for pharmaceutical researchers delving into innovative drug development pathways. Moreover, it seeks to address the intricate challenges confronted by clinical practitioners in managing this incapacitating condition.

Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.

Role of phosphate dysmetabolism in the pathogenesis of chronic fatigue syndrome

Oxidative phosphorylation is a fundamental process of brain energy metabolism. It provides nearly all of the ATP used then in multiple phosphorylation cycles, including glucose phosphorylation. Moderate (40%) efficiency of the glucose ATP cycle requires a continuous extracellular supply of phosphates which deficiency is manifested as chronic fatigue

The efficacy and safety of moxibustion for chronic fatigue syndrome: A protocol for systematic review and meta-analysis.

Background:The pathogenesis of chronic fatigue syndrome (CFS) is not clear. The main purpose of treatment is to improve autoimmune function and relieve fatigue symptoms. Moxibustion is often used to treat diseases caused by low autoimmunity, especially in relieving fatigue symptoms. It is a superior therapy for CFS in traditional Chinese medicine. At present, there is a lack of the high level clinical evidence to support the moxibustion in the treatment of CFS, so this study will systematically review and analyze the currently available randomized controlled trials to evaluate the efficacy and safety of moxibustion in the treatment of CFS.Methods:We will systematically search PubMed, EMBASE, Cochrane library, Sinomed, CNKI, VIP, and Wanfang Database, ClinicalTrials.gov and Chinese Clinical Trial Registry will also be searched. The time range for the search will be from database activation to March 31, 2021. The randomized controlled trials (RCTs) associated with moxibustion for CFS will be included, regardless of language.We will use the standard proposed in Cochrane Handbook 5.1.0 to assess the bias risk of a single RCT. The main outcome index of the study is Fatigue Assessment Instrument (FAI), secondary outcome indexes will include Fatigue Scale -14 (FS-14), Fatigue Severity Scale (FSS), Pittsburgh sleep quality index (PSQI), natural killer (NK) cells, interleukin- 2 (IL-2), T lymphocyte subsets (CD4+, CD8+), cure rate, total efficiency and adverse reactions. The random effect model meta was used to analyze the effect data of a single RCT. Heterogeneity will be measured by Cochran Q test and I-squared statistics. We will use 2 subgroup analyses to explore the source of heterogeneity. RCTs with high bias risk was excluded and adjustment effect model was used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias included in RCTs will be assessed by funnel plot and Egger test.Results:This study will objectively and comprehensively evaluate the efficacy and safety of randomized controlled trials of moxibustion in the treatment of chronic fatigue syndrome, and the results will be submitted to peer-reviewed journals for publication.Conclusion:This systematic review will provide clinicians with the latest high-quality evidence for the use of moxibustion in the treatment of chronic fatigue syndrome.INPLASY registration number:INPLASY202140063.

Advances in Clinical Research on Traditional Chinese Medicine Treatment of Chronic Fatigue Syndrome.

Chronic fatigue syndrome (CFS) is one of the most common chronic diseases in modern society and affects patients' quality of life to a certain extent. To date, the etiology and pathogenesis of CFS are still not completely clear. Various therapies have been developed, but there is still a lack of specific drugs or treatments. As a kind of adjuvant therapy, traditional Chinese medicine (TCM) has aroused widespread concern about the improvement of CFS. Although a large number of clinical randomized controlled trials have confirmed the therapeutic effect of TCM on CFS, the exact efficacy is still controversial. This article summarizes the clinical research methods and efficacy of TCM in the treatment of CFS over the past five years from the perspectives of syndrome differentiation, external treatment, and combination therapy.

Neuroinflammation, Oxidative Stress, and Neurogenesis in a Mouse Model of Chronic Fatigue Syndrome, and the Treatment with Kampo Medicine

The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine. A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1β, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays. The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1β, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1β, IL-6, and IFN-γ in the hippocampus but not in the cortex. The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.

MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome.

Numerous experimental models have shown that microRNAs (miRNAs)play an important role in regulating pain processing in clinical pain disorders. In this study, we evaluated a set of miRNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS). We then correlated the expression of these miRNAs with the levels of inflammatory markers and pain-related comorbidities in adolescents with CFS and healthy controls (HCs). A total of 150 adolescents, 12 to 18years of age, participated in this study between April 2016 and April 2017. The participants were classified into 2 groups: adolescents with CFS (n=100) and HCs (n=50). Reverse-transcription polymerase chain reaction was used to evaluate the expression of miR-558, miR-146a, miR-150, miR-124, and miR-143. Immunoassay analysis was used to assess the levels of immune inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Adolescents with CFS showed significantly higher pain thresholds than comparable nonfatigued HCs. Ability to enjoy life and relations with others were the parameters least influenced by pain in CFS patients. Differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143 was significantly downregulated and notably interfered with pain intensity and frequency in patients with CFS. Also, the expression of these miRNAs was significantly correlated with that of IL-6, TNF-α, and COX-2, which have been shown to mediate pain intensity in patients with CFS. Girls with CFS showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CFS. Girls with CFS also showed increased expression of the inflammatory pain-related markers IL-6, TNF-α, and COX-2 compared with the levels of boys with CFS. The intensity and consequences of pain were influenced by differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143, which was directly associated with higher expression of the immune inflammatory-related genes TNFα, IL-6, and COX-2 in adolescents with CFS. Further studies of larger patient cohorts will help clarify the role of miRNAs in the pathogenesis of CFS.

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

The role of immune or infective triggers in the pathogenesis of Chronic Fatigue Syndrome (CFS) is not yet fully understood. Barriers to obtaining immune measures at baseline (i.e., before the trigger) in CFS and post-infective fatigue model cohorts have prevented the study of pre-existing immune dysfunction and subsequent immune changes in response to the trigger.This study presents interferon-alpha (IFN-α)-induced persistent fatigue as a model of CFS. IFN-α, which is used in the treatment of chronic Hepatitis C Virus (HCV) infection, induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation. This model allows for the assessment of patients before and during exposure to the immune trigger, and afterwards when the original trigger is no longer present.Fifty-five patients undergoing IFN-α treatment for chronic HCV were assessed at baseline, during the 6–12 months of IFN-α treatment, and at six-months post-treatment. Measures of fatigue, cytokines and kynurenine pathway metabolites were obtained. Fifty-four CFS patients and 57 healthy volunteers completed the same measures at a one-off assessment, which were compared with post-treatment follow-up measures from the HCV patients.Eighteen patients undergoing IFN-α treatment (33%) were subsequently defined as having ‘persistent fatigue’ (the proposed model for CFS), if their levels of fatigue were higher six-months post-treatment than at baseline; the other 67% were considered ‘resolved fatigue’. Patients who went on to develop persistent fatigue experienced a greater increase in fatigue symptoms over the first four weeks of IFN-α, compared with patients who did not (Δ Treatment Week (TW)-0 vs. TW4; PF: 7.1 ± 1.5 vs. RF: 4.0 ± 0.8, p = 0.046). Moreover, there was a trend towards increased baseline interleukin (IL)-6, and significantly higher baseline IL-10 levels, as well as higher levels of these cytokines in response to IFN-α treatment, alongside concurrent increases in fatigue. Levels increased to more than double those of the other patients by Treatment Week (TW)4 (p = 0.011 for IL-6 and p = 0.001 for IL-10). There was no evidence of an association between persistent fatigue and peripheral inflammation six-months post-treatment, nor did we observe peripheral inflammation in the CFS cohort. While there were changes in kynurenine metabolites in response to IFN-α, there was no association with persistent fatigue. CFS patients had lower levels of the ratio of kynurenine to tryptophan and 3-hydroxykynurenine than controls.Future studies are needed to elucidate the mechanisms behind the initial exaggerated response of the immune system in those who go on to experience persistent fatigue even if the immune trigger is no longer present, and the change from acute to chronic fatigue in the absence of continued peripheral immune activation.

New Diagnostic Biomarkers for Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without symptoms of infection or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months. The pathogenesis of CFS is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of CFS and diagnostic uncertainty. We performed comprehensive metabolomic analyses of blood samples obtained from patients with CFS and healthy controls to establish an objective diagnosis of CFS. Here, we review previous findings concerning the immune, endocrine, and metabolic system in animal models for CFS and the patients, and present our results which may contribute to the development of a diagnostic biomarker for CFS.

Chronic Fatigue Syndrome: A Critical Review

Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME), is a challenge to physicians. CFS prevalence is below 1 % in a general population. There are no convincing models that might explain etiology and pathogenesis of CFS as an independent, unique disease. No consistent diagnostic criteria are available. In the differential diagnosis of chronic fatigue, a variety of somatic (e. g. chronic infectious diseases, multiple sclerosis, endocrinological disorders) and psychiatric/psychosomatic diseases should be considered. After exclusion of somatic causes, there is a significant overlap with major depression and somatoform disorders. Exercise therapy, antidepressants and psychotherapy are useful treatment options. Unless there is enough evidence for neuroinflammation, aggressive immunotherapies like rituximab should not be considered. In sum, there is not enough evidence to assume that CFS is an independent, unique disease.

Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome.

BackgroundThe NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue.MethodsWe established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated.ResultsMice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1β and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1β production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1β levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1β levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were not significantly altered.ConclusionsThese findings suggest that LPS-induced fatigue is an IL-1β-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0539-1) contains supplementary material, which is available to authorized users.

Lipid Replacement Therapy: Is it a New Approach in Patients with Chronic Fatigue Syndrome?

Lipid replacement therapy (LRT) is an anti-aging product which reverses age-related changes in the lipid composition of organ and tissue cells. Since membrane lipids oxidation seems to be involved in the pathogenesis of Chronic Fatigue Syndrome (CFS), their substitution with new lipids coming from dietary supplements is speculated to be effective in CFS. We have analyzed some of the most recent articles about the effects of LRT in fatigue, showing the evidences supporting this theory as well as alluding to the weak points of the studies.

A Study of the Protective Effect of Triticum aestivum L. in an Experimental Animal Model of Chronic Fatigue Syndrome.

Background:Oxidative stress plays a major role in the pathogenesis of chronic fatigue syndrome (CFS). Keeping in view the proven antioxidant activity of Triticum aestivum L., this study has been undertaken to explore the potential therapeutic benefit of this plant in the treatment of CFS.Objective:To study the protective effect of the ethanolic extract of the leaves of Triticum aestivum (EETA) in an experimental mice model of CFS.Materials and Methods:Five groups of albino mice (20-25 g) were selected for the study, with five animals in each group. Group A served as the naïve control and Group B served as the stressed control. Groups C and D received EETA (100 mg/kg and 200 mg/kg b.w.). Group E received imipramine (20 mg/kg b.w.). Except for Group A, mice in each group were forced to swim 6 min each for 7 days to induce a state of chronic fatigue. Duration of immobility was measured on every alternate day. After 7 days, various behavioral tests (mirror chamber and elevated plus maize test for anxiety, open field test for locomotor activity) and biochemical estimations (malondialdehyde [MDA] and catalase activity) in mice brain were performed.Results:Forced swimming in the stressed group resulted in a significant increase in immobility period, decrease in locomotor activity and elevated anxiety level. The brain homogenate showed significantly increased MDA and decreased catalase levels. The extract-treated groups showed significantly (P < 0.05) improved locomotor activity, decreased anxiety level, elevated catalase levels and reduction of MDA.Conclusion:The study confirms the protective effects of EETA in CFS.

Dysregulation of the HPA Axis in Chronic Fatigue Syndrome

A wide array of physiologic mechanisms has been proposed to explain the symptomatology and pathogenesis of chronic fatigue syndrome. One consistent finding points to potential disruptions of hypothalamic-pituitary-adrenal (HPA) axis functioning concomitant with hypocortisolism. While there are divergent theories, evidence has been found for a possible lack of responsiveness on the part of the HPA axis to challenge, a pattern of glucocorticoid resistance, and disruption or dysregulation of the expected diurnal cortisol pattern among patients with CFS. Some authors offer that CFS is the result of a maladaptive stress response, one that is under the influence of genetic variance or epigenetic influences. Recent research demonstrates a lack of messenger RNA encoding for the glucocorticoid receptor, with evidence pointing toward histone deacetylases. The intent of this review is to highlight these findings supporting dysregulation of the HPA axis in CFS.

Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by tiredness, difficulty in concentration and memory, and concomitant skeletal and muscular pain, thus affecting both mental and physical domains. The pathogenesis of chronic fatigue syndrome is multifactorial and involves increased oxido-nitrosative stress along with generation of pro-inflammatory cytokines such as TNF-α. In the present study chronic fatigue was produced in rats by plunging a load of 10±2% body weight and subjecting them to forced swim inside a rectangular jar daily for 28 days. Endurance capacity and post-swim fatigue were assessed on 1st, 7th, 14th, 21st and 28th days. EGCG was administered daily by oral gavage 30min before forced swim session. On the 29th day, after assessment of various behavioral parameters, blood was collected through tail vein, and animals were sacrificed to harvest the brains, spleens and thymus. Chronic fatigue group exhibited significant behavioral alterations along with enhanced oxido-nitrosative stress and serum TNF-α level as compared to naive group. Chronic treatment with EGCG restored all the behavioral and biochemical alterations associated with chronic fatigue syndrome. The present study signifies the therapeutic potential of EGCG for the treatment of chronic fatigue syndrome.

Chronic fatigue syndrome – A neuroimmunological model

The aetiological and pathophysiological basis of chronic fatigue syndrome (CFS) remains a controversial field of inquiry in the research community. While CFS and similar disease conditions such as fibromyalgia (FM) and post-infectious encephalopathy have been the focus of intense scrutiny for the past 20 years, results of research were often contradictory and a cohesive pathological model has remained elusive. However, recent developments in understanding the unique immunophysiology of the brain may provide important clues for the development of a truly comprehensive explanation of the pathology of CFS. We argue that CFS pathogenesis lies in the influence of peripheral inflammatory events on the brain and the unique immunophysiology of the central nervous system. There is also evidence that CFS patients have a relative immunodeficiency that predisposes to poor early control of infection that leads to chronic inflammatory responses to infectious insults. The neurological and endocrine changes have been described in CFS patients support the view that CFS has an inflammatory pathogenesis when considered as a whole. An inflammatory model of disease also provides an explanation for the marked female sex bias associated with CFS. This review therefore posits the hypothesis that CFS as a disease of long-term inflammatory processes of the brain. We will also provide an investigative framework that could be used to justify the use of anti-TNF biological agents as a reliable and effective treatment approach to CFS, a syndrome that to date remains frustratingly difficult for both patients and health care professionals to manage.

Self-Critical Perfectionism, Stress Generation, and Stress Sensitivity in Patients with Chronic Fatigue Syndrome: Relationship with Severity of Depression

Chronic Fatigue Syndrome (CFS) is a highly disabling disorder that is part of a broader spectrum of chronic pain and fatigue disorders. Although the etiology and pathogenesis of CFS largely remain unclear, there is increasing evidence that CFS shares important pathophysiological disturbances with mood disorders in terms of disturbances in the stress response and the stress system. From a psycho-dynamic perspective, self-critical perfectionism and related personality factors are hypothesized to explain in part impairments of the stress response in both depression and CFS. Yet, although there is ample evidence that high levels of self-critical perfectionism are associated with stress generation and increased stress sensitivity in depression, evidence supporting this hypothesis in CFS is currently lacking. This study therefore set out to investigate the relationship between self-critical perfectionism, the active generation of stress, stress sensitivity, and levels of depression in a sample of 57 patients diagnosed with CFS using an ecological momentary assessment approach. Results showed, congruent with theoretical assumptions, that self-critical perfectionism was associated with the generation of daily hassles, which in turn predicted higher levels of depression. Moreover, multilevel analyses showed that self-critical perfectionism was related to increased stress sensitivity in CFS patients over a 14-day period, and that increased stress sensitivity in turn was related to increased levels of depression. The implications of these findings for future research and particularly for the development of psychodynamic treatment approaches of CFS and related conditions are discussed.

Sleep and fatigue in mice infected with murine gammaherpesvirus 68

Fatigue, a common symptom of many acute and chronic medical conditions, reduces both quality of life and workplace productivity and can be disabling. However, the pathophysiologic mechanisms that underlie fatigue can be difficult to study in human populations due to the patient heterogeneity, the variety of underlying causes and potential triggering events, and an inability to collect samples that may be essential to elucidation of mechanisms (e.g., brain). Although the etiology of chronic fatigue syndrome (CFS) remains elusive, some studies have implicated viral infections, including Epstein-Barr virus (EBV), a human gammaherpesvirus, as a potential factor in the pathogenesis of CFS. Murine gammaherpesvirus 68 (γHV68) is a mouse pathogen that shares many similarities with human γHVs, including EBV. In this study, we use γHV68-infected C57BL/6J mice as a model system for studying the impact of chronic viral infection on sleep–wake behavior, activity patterns, and body temperature profiles. Our data show that γHV68 alters sleep, activity, and temperature in a manner suggestive of fatigue. In mice infected with the highest dose used in this study (40,000plaque forming units), food intake, body weight, wheel running, body temperature, and sleep were normal until approximately 7days after infection. These parameters were significantly altered during days 7 through 11, returned to baseline levels at day 12 after infection, and remained within the normal range for the remainder of the 30-day period after inoculation. At that time, both infected and uninfected mice were injected with lipopolysaccharide (LPS), and their responses monitored. Uninfected mice given LPS developed a modest and transient febrile response during the initial light phase (hours 12 through 24) after injection. In contrast, infected mice developed changes in core body temperatures that persisted for at least 5days. Infected mice showed an initial hypothermia that lasted for approximately 12h, followed by a modest fever that persisted for several hours. For the remainder of the 5-day recording period, they showed mild hypothermia during the dark phase. Running wheel activity of infected mice was reduced for at least 5days after injection of LPS, but for only 12h in uninfected mice. Collectively, these observations indicate that (1) physiologic and behavioral processes in mice are altered and recover during an early phase of infection, and (2) mice with latent γHV68 infection have an exacerbated response to challenge with LPS. These findings indicate that laboratory mice with γHV68 infections may provide a useful model for the study of fatigue and other physiologic and behavioral perturbations that may occur during acute and chronic infection with gammaherpesviruses.

A review of the definitional criteria for chronic fatigue syndrome

The research community has for more than three decades tried to unravel the diagnostic mystery that is Chronic Fatigue Syndrome (CFS). This has resulted in considerable amounts of time and money being invested in attempts aimed at establishing the aetiology and pathogenesis of CFS. All of this investment has produced evidence of an interesting variety of endocrine, immune, infectious, muscular and neurological abnormalities in CFS; however, the cause remains elusive. The absence of a known causative agent or diagnostic test for CFS has resulted in the development of a number of CFS case definitions. As such, the main objectives of this paper are to provide a critical review of the similarities and differences between the varying approaches to CFS case definition. The conflicts and controversies that have emerged as a result of the differing definitional criterion for CFS are highlighted and the potential impact on future research is identified. This paper presents a critical review of the most frequently used case definitions in CFS. There are currently five case definitions of CFS; however, the most prominent and widely used of these definitions is the 1994 Centre for Disease Control and Prevention Case Definitions. However, the pre-eminence of this definition over the others has never been substantiated and it has been widely criticized for its lack of specificity. Furthermore, none of the above case definitions have produced evidence to demonstrate their accuracy or precision at defining cases of CFS. A summary description of the symptom profile included in each of the case definitions is provided. The inconsistencies that have emerged in CFS research as a consequence of differing approaches to case definition are also highlighted and discussed.

Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome

BackgroundRecent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (XMRV) contributes to the pathogenesis of chronic fatigue syndrome (CFS). To investigate the question in a Chinese population, 65 CFS patients and 85 blood donor controls were enrolled and multiplex real-time PCR or reverse transcriptase PCR (RT-PCR) was developed to analyze the XMRV infection status of the study participants. The assay was standardized by constructing plasmid DNAs and armored RNAs as XMRV standards and competitive internal controls (CICs), respectively.ResultsThe sensitivities of the multiplex real-time PCR and RT-PCR assays were 20 copies/reaction and 10 IU/ml, respectively, with 100% specificity. The within-run precision coefficient of variation (CV) ranged from 1.76% to 2.80% and 1.70% to 2.59%, while the between-run CV ranged from 1.07% to 2.56% and 1.06% to 2.74%. XMRV was not detected in the 65 CFS patients and 65 normal individuals out of 85 controls.ConclusionsThis study failed to show XMRV in peripheral blood mononuclear cells (PBMCs) and plasma of Chinese patients with CFS. The absence of XMRV nucleic acids does not support an association between XMRV infection and the development of CFS in Chinese.