Inflammation Studies

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Extended List of Studies (by year)

2015-2019

Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study. [Full Text] [PDF]
Castro-Marrero J, Serrano-Pertierra E, Oliveira-Rodríguez M, Zaragozá MC, Martínez-Martínez A, Blanco-López MDC, Alegre J. J Extracell Vesicles. 2018

Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case-control study.
[Full Text] [PDF]
Clark LV, Buckland M, Murphy G, Taylor N, Vleck V, Mein C, Wozniak E, Smuk M, White PD. Clin Exp Immunol. 2017

Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology.
[Full Text] [PDF]
Halpin P, Williams MV, Klimas NG, Fletcher MA, Barnes Z, Ariza ME. J Med Virol. 2017

Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations. [Full Text] [PDF]
Hornig M, Gottschalk CG, Eddy ML, Che X, Ukaigwe JE, Peterson DL, Lipkin W. Transl Psychiatry. 2017

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray.
[Full Text] [PDF]
Loebel M, Eckey M, Sotzny F, Hahn E, Bauer S, Grabowski P, Zerweck J, Holenya P, Hanitsch LG, Wittke K, Borchmann P, Rüffer JU, Hiepe F, Ruprecht K, Behrends U, Meindl C, Volk HD, Reimer U, Scheibenbogen C.
PLoS One. 2017

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women.
[Full Text] [PDF]
Milrad SF, Hall DL, Jutagir DR, Lattie EG, Ironson GH, Wohlgemuth W, Nunez MV, Garcia L6, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. J Neuroimmunol. 2017

[HIGHLIGHT] Cytokine signature associated with disease severity in chronic fatigue syndrome patients. [Full Text] [PDF]
Montoya G, Holmes TH, Anderson JN, Maecker HT, Rosenberg-Hasson Y, Valencia IJ, Chu L, Younger J, Tato CM, Davis MM. Proc Natl Acad Sci U S A. 2017
The presence of ongoing or fluctuating flu-like symptoms, arthralgias, myalgias, autonomic disturbances, and a striking hypersensitivity to stimuli in many patients with this illness has led to the suspicion that ME/CFS is an inflammatory or immunological disorder...Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease.

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways.
Morris G, Anderson G, Maes M. Mol Neurobiol. 2017

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. [Full Text] [PDF]
Nguyen CB, Alsøe L, Lindvall JM, Sulheim D, Fagermoen E, Winger A, Kaarbø M, Nilsen H, Wyller VB.
J Transl Med. 2017

Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels. [Full Text] [PDF]
Nguyen T, Johnston S, Clarke L, Smith P, Staines D, Marshall-Gradisnik S. Clin Exp Immunol. 2017

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. [Full Text] [PDF]
Theorell J, Bileviciute-Ljungar I, Tesi B, Schlums H, Johnsgaard MS, Asadi-Azarbaijani B, Bolle Strand E, Bryceson YT. Front Immunol. 2017

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis. [Full Text] [PDF]
Huth TK, Brenu EW, Ramos S, Nguyen T, Broadley S, Staines D, Marshall-Gradisnik S.  Scand J Immunol. 2016
Co-expression of CD57 and perforin was significantly increased on CD56(dim) CD16(+) NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome. [PDF]
Landi A, et al. Cytokine. 2016

Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients. [PDF]
Nguyen T, et al. Biol Res. 2016

Illness progression in chronic fatigue syndrome: a shifting immune baseline. [Full Text] [PDF]
Russell L, Broderick G, Taylor R, Fernandes H, Harvey J, Barnes Z, Smylie A, Collado F, Balbin EG, Katz BZ, Klimas NG, Fletcher MA. BMC Immunol. 2016
Preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

Chronic fatigue syndrome and circulating cytokines: A systematic review.
Blundell S, et al. Brain Behav Immun. 2015

Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. [PDF]
Hardcastle SL, Brenu EW, Johnston S, Nguyen T, Huth T, Ramos S, Staines D, Marshall-Gradisnik S. Int J Med Sci. 2015
IL-1β was significantly reduced in severe compared with moderate CFS/ME patients. IL-6 was significantly decreased in moderate CFS/ME patients compared with healthy controls and severe CFS/ME patients. RANTES was significantly increased in moderate CFS/ME patients compared to severe CFS/ME patients. Serum IL-7 and IL-8 were significantly higher in the severe CFS/ME group compared with healthy controls and moderate CFS/ME patients. IFN-γ was significantly increased in severe CFS/ME patients compared with moderately affected patients.

Distinct plasma immune signatures in ME/CFS are present early in the course of illness. [PDF]
Hornig M, et al. Sci Adv. 2015

[HIGHLIGHT] Cytokines in the cerebrospinal fluids of patients with chronic fatigue syndrome/myalgic encephalomyelitis.
[PDF]
Peterson D, et al. Mediators Inflamm. 2015
This preliminary investigation suggests that perturbations in inflammatory cytokines in the CSF of CFS/ME patients may contribute to the neurological discrepancies observed in CFS/ME.

[HIGHLIGHT] Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity [PDF]
Strayer D, Scott V, Carter W. Journal of Clinical & Cellular Immunology. 2015
An important future research direction in CFS is to develop safe
and effective therapy for this severely debilitated and chronically ill patient population. Low NK cell activity is commonly seen in CFS and is associated with increased symptom severity. Thus, low NKCC in CFS provides an important clue to the pathophysiology of the illness. Approaches to safety augment NKCC in this subset of CFS patients should be explored.

2010-2014

DNA methylation modifications associated with chronic fatigue syndrome. [PDF]
de Vega WC, et al. PLoS One. 2014

[HIGHLIGHT] Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). [PDF]
Morris G, et al. Curr Neuropharmacol. 2014
Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels.

Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease.

The Glutathione System: A New Drug Target in Neuroimmune Disorders. [Full Text]
Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M, Maes M. Mol Neurobiol. 2014
Glutathione depletion and concomitant increase in oxidative and nitrosative stress pathways as well as mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson’s disease, suggesting that depleted GSH is an integral part of these diseases.

Could mitochondrial dysfunction be a differentiating marker between Chronic Fatigue Syndrome and Fibromyalgia? [Full Text]
Castro-Marrero J, Cordero MD, Saez-Francas N, Jimenez-Gutiérrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Antioxid Redox Signal. 2013
Peripheral blood mononuclear cells (PBMC) showed decreased levels of CoQ10 and ATP from CFS and FM subjects compared to controls. CFS/FM patients had significantly increased levels of lipid peroxidation, indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity, mitochondrial DNA content (mtDNA/gDNA ratio) and expression levels of PGC-1α and TFAM were significantly lower in FM patients than in controls.

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome
[PDF]
Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J. J Transl Med. 2013

Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome.
Maes M. Mod Trends Pharmacopsychiatry. 2013.

The Emerging Role of Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
[Full Text] [PDF]
Morris G, Berk M, Galecki P, Maes M. Mol Neurobiol. 2013
Abnormalities in ME/CFS include elevated oxidative and nitrosative stress (O&NS), activation of immuno-inflammatory pathways, and mitochondrial dysfunctions with depleted levels of adenosine triphosphate (ATP) synthesis. There is also evidence that many patients with ME/CFS (up to around 60%) may suffer from autoimmune responses. This paper reviews the potential sources of the autoimmunity.

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. [PDF]
Smylie AL, et al. BMC Immunol. 2013

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. [PDF]
Brenu EW, van Driel ML, Staines DR, Ashton KJ, Hardcastle SL, Keane J, Tajouri L, Peterson D, Ramos SB, Marshall-Gradisnik SM. J Transl Med. 2012
This study’s results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue. [Full Text] [PDF]
Broderick G, Katz BZ, Fernandes H, Fletcher MA, Klimas N, Smith FA, O’Gorman MR, Vernon SD, Taylor R. J Transl Med. 2012
Researchers measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in CFS patients vs. controls. Study results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

[HIGHLIGHT] Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. [Full Text]
Maes M, Twisk FN, Kubera M, Ringel K. J Affect Disord. 2012
The findings show that ME/CFS is characterized by low-grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFα.

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. [PDF]
Brenu EW, et al. J Transl Med. 2011

Lipid peroxidation is elevated in female patients with chronic fatigue syndrome. [Full Text] [PDF]
Brkic S, Tomic S, Maric D, Novakov Mikic A, Turkulov V. Med Sci Monit. 2010
CFS is associated with lipid peroxidation and oxidative stress.  High levels of malondialdehyde, positively correlated with total cholesterol and lower HDL cholesterol levels, might be indicative of proatherogenic events in female CFS patients.

A formal analysis of cytokine networks in Chronic Fatigue Syndrome. [Full Text] [PDF]
Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA. Brain Behav Immun. 2010
CFS patients have specific immune responses related to the presence of inflammatory processes consistent with the presence of a latent viral infection.

Biomarkers in Chronic Fatigue Syndrome: Evaluation of Natural Killer Cell Function and Dipeptidyl Peptidase IV/CD26 [PDF]
Fletcher MA,  Zeng XR, Maher K, Levis S, Hurwitz B, Antoni M, Broderick G, Klimas NG. PLoS One. 2010

Biochemical and vascular aspects of pediatric chronic fatigue syndrome.
Kennedy G, Khan F, Hill A, Underwood C, Belch JJ. Arch Pediatr Adolesc Med. 2010
Biomedical anomalies seen in adults with CFS/ME-increased oxidative stress and increased white blood cell apoptosis-can also be observed in children with clinically diagnosed CFS/ME compared with matched controls.

Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. [Full Text]
Miwa K, Fujita M. Heart Vessels. 2010
CFS patients have lower levels of Vitamin E (and therefore possible greater oxidative stress) during times of exacerbation than during times of remission.

Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome. [PDF]
White AT, et al. Psychophysiology. 2010

2005-2009

Plasma cytokines in women with chronic fatigue syndrome. [Full Text] [PDF]
Fletcher MA, Zeng XR, Barnes Z, Levis S, Klimas NG. J Transl Med. 2009
CFS patients display a large number of abnormal cytokines, with increases in some (LTalpha, IL-1alpha, IL-1beta, IL-4, IL-5, IL-6 and IL-12) and decreases in others (IL-8, IL-13 and IL-15).  Some of these have the potential of serving as biomarkers for the disease.

Chronic fatigue syndrome and complement activation. [PDF]
Geller RD, Giclas PC. BMJ Case Rep. 2009
This report describes a case of chronic fatigue syndrome (CFS) that followed a well-documented episode of acute Epstein-Barr virus (EBV) mononucleosis. After 2 years of chronic fatigue following the acute illness, measurements of complement split products were positive for complement activation and remained positive for 14 months, after which the patient then recovered from CFS.

Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.
[Full Text] [PDF]
Jason LA, Porter N, Herrington J, Sorenson M, Kubow S. J Behav Neurosci Res. 2009
CFS can affect the immune, neuroendocrine, autonomic, and neurologic systems. Abnormal biological findings among some patients have included aberrant ion transport and ion channel activity, cortisol deficiency, sympathetic nervous system hyperactivity, EEG spike waves, left ventricular dysfunction in the heart, low natural killer cell cytotoxicity, and a shift from Th1 to Th2 cytokines. We propose that the kindling and oxidative stress theories provide a heuristic template for better understanding of this illness.

Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS.
Maes M, Twisk FN. Neuro Endocrinol Lett. 2009
Previous reports suggest that CFS patients dying of heart failure do so at a significantly lower age than non-patients (59 years vs. 83 years). A number of abnormalities in CFS may be responsible for this, including: a) chronic low grade inflammation with extended production of nuclear factor kappa B and COX-2 and increased levels of tumour necrosis factor alpha; b) increased O&NS with increased peroxide levels, and phospholipid oxidation including oxidative damage to phosphatidylinositol; c) decreased levels of specific antioxidants, i.e. coenzyme Q10, zinc and dehydroepiandrosterone-sulphate; d) bacterial translocation as a result of leaky gut; e) decreased omega-3 polyunsatutared fatty acids (PUFAs), and increased omega-6 PUFA and saturated fatty acid levels; and f) the presence of viral and bacterial infections and psychological stressors.

Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients. [Full Text]
Metzger K, Frémont M, Roelant C, De Meirleir K. Biochem Biophys Res Commun. 2008
T helper 17 (Th17) cells belong to a recently identified subset of T helper cells, with crucial regulatory function in inflammatory and autoimmune processes. Th17 cells are implicated in allergic inflammation, intestinal diseases, central nervous system inflammation, disorders that may all contribute to the pathophysiology of CFS. IL-17F is one of the pro-inflammatory cytokines secreted by Th17 cells. The results suggest a role of Th17 cells in the pathogenesis of CFS.

Specific correlations between muscle oxidative stress and chronic fatigue syndrome: a working hypothesis.
[Full Text] [PDF]
Fulle S, Pietrangelo T, Mancinelli R, Saggini R, Fanò G. J Muscle Res Cell Motil. 2007
The role of oxidative stress in CFS is an emerging focus of research due to evidence of its association with some pathological features of this syndrome. New data collectively support the presence of specific critical points in the muscle that are affected by free radicals.

Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells.
Mihaylova I, et al. Neuro Endocrinol Lett. 2007

Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. [PDF]
Maes M, Mihaylova I, Leunis JC.  Neuro Endocrinol Lett. 2006
CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic.

Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. [PDF]
Maes M, Mihaylova I, De Ruyter M. J Affect Disord. 2006
CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways. Since zinc is a strong anti-oxidant, the present results further support the findings that CFS is accompanied by increased oxidative stress.

Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup? [Full Text]
Siegel SD, Antoni MH, Fletcher MA, Maher K, Segota MC, Klimas N. J Psychosom Res. 2006
Relative to CFS patients with normal Natural Killer Cell Activity (NKCA), low-NKCA patients reported less vigor, more daytime dysfunction, and more cognitive impairment. In addition, low-NKCA patients performed less on objective measures of cognitive functioning relative to normal-NKCA patients.

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome.
[PDF]
Gaab J, Rohleder N, Heitz V, Engert V, Schad T, Schürmeyer TH, Ehlert U. Psychoneuroendocrinology. 2005
Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. TNF-alpha and IL-6 were especially problematic.

Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?
Nijs J, Van de Velde B, De Meirleir K. Med Hypotheses. 2005
It is hypothesised that a nitric oxide (NO)-dependent reduction in inhibitory activity of the central nervous system and consequent central sensitisation accounts for chronic widespread pain in CFS patients.

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression. [Full Text] [PDF]
Robertson MJ, Schacterle RS, Mackin GA, Wilson SN, Bloomingdale KL, Ritz J, Komaroff AL.
Clin Exp Immunol. 2005
Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells.

2000-2004

High levels of type 2 cytokine-producing cells in chronic fatigue syndrome. [PDF]
Skowera A, Cleare A, Blair D, Bevis L, Wessely SC, Peakman M. Clin Exp Immunol. 2004
The authors found evidence of a significant bias towards Th2- and Tc2-type immune responses in CFS compared to controls. In contrast, levels of IFN-gamma, IL-2 and IL-10-producing cells were similar in both study groups. There is an effector memory cell bias towards type 2 responsiveness in patients with CFS, as well as ongoing type 0 immune activation in unstimulated cultures of peripheral blood cells.

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. [Full Text] [PDF]
Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA. Neurosci Lett. 2003
Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS.

Cytokine responses to physical activity, with particular reference to IL-6: sources, actions, and clinical implications.
Shephard RJ. Crit Rev Immunol. 2002
Prolonged endurance exercise induces a sequenced release of pro- and anti-inflammatory cytokines, and IL-6 plays a dominant role. Although many types of cells are capable of producing cytokines, the main source of the exercise-induced IL-6 production appears to be the exercising muscle.

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. [Full Text] [PDF]
Kerr JR, Barah F, Mattey DL, Laing I, Hopkins SJ, Hutchinson IV, Tyrrell DA. J Gen Virol. 2001
Patients with a parvovirus B19 infection had elevated IL-6, TNF-alpha, IL-1 beta, and IFN-gamma.

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. [Full Text]
Fulle S, Mecocci P, Fanó G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF. Free Radic Biol Med. 2000
The authors detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels.

Pre-2000

Acute phase responses and cytokine secretion in chronic fatigue syndrome.
Cannon JG, et al. J Clin Immunol. 1999

Dysfunction of natural killer activity in a family with chronic fatigue syndrome.
Levine PH, Whiteside TL, Friberg D, Bryant J, Colclough G, Herberman RB. Clin Immunol Immunopathol. 1998
Low NK activity some families may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.

Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome. [Full Text]
Ogawa M, Nishiura T, Yoshimura M, Horikawa Y, Yoshida H, Okajima Y, Matsumura I, Ishikawa J, Nakao H, Tomiyama Y, Kanayama Y, Kanakura Y, Matsuzawa Y. Eur J Clin Invest. 1998
In healthy control subjects, NK activity was significantly increased after treatment with L-Arg, an NK function enhancer, for 24 h, whereas the same treatment failed to enhance NK activity in the CFS patients. Further study results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients.

Natural killer cells and natural killer cell activity in chronic fatigue syndrome. [Full Text] [PDF]
Whiteside TL, Friberg D. Am J Med. 1998
Low levels of natural killer cell activity have been reported in a significant percentage of cases in CFS.

Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.
Regland B, Andersson M, Abrahamsson L, Bagby J, Dyrehag LE, Gottfries CG. Scand J Rheumatol. 1997
In all the subjects in a group of patients having both CFS and fibromyalgia, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15.

Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome.
Ojo-Amaize EA, Conley EJ, Peter JB. Clin Infect Dis. 1994
This data suggest a correlation between low levels of natural killer cell activity and severity of CFS.

Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression.
Patarca R, Klimas NG, Lugtendorf S, Antoni M, Fletcher MA. Clin Infect Dis. 1994
CFS patients had higher circulating levels of TNF-alpha and TNF-beta than controls.

Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.
[Full Text] [PDF]
Peterson PK, Sirr SA, Grammith FC, Schenck CH, Pheley AM, Hu S, Chao CC. Clin Diagn Lab Immunol. 1994
At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in CFS patients. Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated post exercise in the CFS group.

Chronic fatigue immune dysfunction syndrome.
Uchida A. Nihon Rinsho. 1992
Restoration of NK activity was correlated with recovery from CFS in patients.

Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. [Full Text]
Caligiuri M, Murray C, Buchwald D, Levine H, Cheney P, Peterson D, Komaroff AL, Ritz J. J Immunol. 1987
A majority of patients with CFS have low numbers of NKH1+T3- lymphocytes, a population that represents the great majority of NK cells in normal individuals. Patients with CFS consistently demonstrated low levels of killing. After activation of cytolytic activity with recombinant interleukin 2, patients were able to display increased killing against K562 but most patients remained unable to lyse Epstein-Barr virus-infected B cell targets. Additional cytotoxicity experiments were carried out utilizing anti-T3 monoclonal antibody to block killing by NKH1+T3+ cells. These experiments indicated that the NK cell that appears to be responsible for much of the functional activity remaining in patients with CFS belongs to the NKH1+T3+ subset, which under normal circumstances represents only approximately 20% of the NK cell population.