Category: Immune System

Chronic fatigue syndrome–a controlled cross sectional study

Abstract:

OBJECTIVE: To look for signs of immunodeficiencies and/or longstanding infections underlying chronic fatigue syndrome (CFS).

METHODS: Twenty-one patients fulfilling the Centers for Disease Control criteria for CFS were compared to 21 age and sex matched controls. A number of viral antibodies as well as the following tests evaluating the immune system were studied: autoantibody profile, cell surface markers on isolated blood mononuclear cells, cytokine production, lymphocyte proliferative responses, natural killer cell activity and quantitation of immunoglobulin secreting cells.

RESULTS: Production in vitro of the predominantly T cell derived cytokines interleukin 2 and interferon gamma was significantly higher in patients with CFS compared to the control group. Furthermore, the serum concentrations of IgA and IgE were lower in patients with CFS; however, this difference was caused by a larger number with values of IgA and IgE above the upper limit of the normal range among the controls than among the patients with CFS. All other variables were similar in the 2 groups.

CONCLUSION: A pathogenically significant imbalance of the immune system in patients with CFS cannot be excluded. However, evidence of a causal link between abnormal immunity and CFS was not obtained.

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. J Rheumatol. 1994 Aug;21(8):1527-31. http://www.ncbi.nlm.nih.gov/pubmed/7983659

 

Chronic fatigue syndrome. Immunological findings vary between populations

Comment on: Longitudinal study of outcome of chronic fatigue syndrome. [BMJ. 1994]

 

Editor,-We were interested in Andrew Wilson and colleagues’ paper investigating predictors of the long term outcome of the chronic fatigue syndrome in patients in Australia. We have investigated the association between immune activation and presumed cutaneous anergy in 68 Scottish patients with the syndrome (19 cases conformed to the Centers for Disease Control’s criteria, 18 cases had been diagnosed by a consultant, 28 cases had been diagnosed by a general practitioner, and three patients referred themselves) and 22 family contacts. We assessed delayed hypersensitivity responses (using Multitest antigens and tuberculin skin tests) and evaluated peripheral blood activation markers (CD8, CD38/ CD llb/HLA-DR) using flow cytometry. Patients were classified into three groups on the basis of current severity of illness and mobility.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540184/pdf/bmj00440-0055b.pdf

 

Source: Abbot NC, Spence VA, Lowe JG, Potts RC, Hassan AH, Belch JJ, Beck JS. Chronic fatigue syndrome. Immunological findings vary between populations. BMJ. 1994 May 14;308(6939):1299. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540184/

 

Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients

 

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS.

Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group.

Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.

 

Source: Peterson PK, Sirr SA, Grammith FC, Schenck CH, Pheley AM, Hu S, Chao CC. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Lab Immunol. 1994 Mar;1(2):222-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/pdf/cdli00002-0112.pdf

 

Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome

Abstract:

Natural killer (NK) cell activity was measured blindly in vitro with blood specimens from 50 healthy individuals and 20 patients with clinically defined chronic fatigue immune dysfunction syndrome (CFIDS) who met the criteria established by the Centers for Disease Control and Prevention (Atlanta).

In accordance with a group scoring system of 1-10 points, with 10 being the most severe clinical status, the patient population was stratified into three clinical groups: A (> 7 points), B (5-7 points), and C (< 5 points). NK cell activity was assessed by the number of lytic units (LU), which for the 50 healthy controls varied between 20 and 250 (50%, 20-50 LU; 32%, 51-100 LU; 6%, 101-130 LU; and 12%, > 150 LU).

In none of the 20 patients with CFIDS was the NK cell activity > 100 LU. For group C, the 10 patients stratified as having the least severe clinical condition, the measure was 61.0 +/- 21.7 LU; for group B (more severe, n = 7), it was 18.3 +/- 7.3 LU; and for group A (most severe, n = 3), it was 8.0 +/- 5.3 LU.

These data suggest a correlation between low levels of NK cell activity and severity of CFIDS, which, if it is confirmed by additional studies of larger groups, might be useful for subgrouping patients and monitoring therapy and/or the progression of CFIDS.

 

Source: Ojo-Amaize EA, Conley EJ, Peter JB. Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S157-9. http://www.ncbi.nlm.nih.gov/pubmed/8148445

 

Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression

Abstract:

Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested.

Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS–but not in controls–serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS.

 

Source: Patarca R, Klimas NG, Lugtendorf S, Antoni M, Fletcher MA. Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis. 1994 Jan;18 Suppl 1:S147-53. http://www.ncbi.nlm.nih.gov/pubmed/8148443

 

Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise

Abstract:

We have studied the relationship between the cytokine production induced in vivo by prolonged isometric exercise and the symptom complex marked by fatigue in patients with chronic fatigue syndrome (CFS).

Twelve male patients and 13 matched male control subjects undertook an isometric hand-grip exercise protocol utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the target force was set at 40% of the maximal voluntary contraction and the duty cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood samples were collected and assayed for the presence of cytokines, including interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis factor-alpha. At those times subjects also completed the Profile of Mood States (POMS) questionnaire, which served as a measure of changes in subjective fatigue.

No significant alteration in the level of any of the cytokines in the plasma of patients or control subjects was detected before, during, or after exercise. Surprisingly, the patients’ levels of fatigue, depression, and confusion, as measured by the POMS, decreased in response to the exercise.

These data do not confirm the presence of an immunologic process correlating with the exacerbation of fatigue after exercise experienced by patients with CFS. Limitations in the study design and in the sensitivity of the cytokine assays may have affected our results.

 

Source: Lloyd A, Gandevia S, Brockman A, Hales J, Wakefield D. Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise. Clin Infect Dis. 1994 Jan;18 Suppl 1:S142-6. http://www.ncbi.nlm.nih.gov/pubmed/8148442

 

Immunologic abnormalities associated with chronic fatigue syndrome

Abstract:

Several aspects of cellular immunity in patients with clinically defined chronic fatigue syndrome (CFS) were evaluated and compared with those in healthy individuals.

Flow cytometric analyses revealed normal expression of total T (CD3+), B (CD19+), and NK (natural killer) (CD16+, CD56+) markers on the surface of peripheral blood mononuclear cells (PMC) from patients with CFS.

However, compared with those of healthy individuals, patients’ CD8+ T cells expressed reduced levels of CD11b and expressed the activation markers CD38 and HLA-DR at elevated levels. In many of the individuals in whom expression of CD11b was reduced the expression of CD28 was increased.

These findings indicate expansion of a population of activated CD8+ cytotoxic T lymphocytes. A marked decrease in NK cell activity was found in almost all patients with CFS, as compared with that in healthy individuals. No substantial abnormalities in monocyte activity or T cell proliferation were observed. The results of this study suggest that immune cell phenotype changes and NK cell dysfunction are common manifestations of CFS.

 

Source: Barker E, Fujimura SF, Fadem MB, Landay AL, Levy JA. Immunologic abnormalities associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S136-41. http://www.ncbi.nlm.nih.gov/pubmed/8148441

 

Viral studies of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has many characteristics suggesting persistent fatigue following a viral illness. At least nine different RNA and DNA viruses have been considered to be associated with this disease, but none of these viruses has been found to be the etiologic agent. Immunologic studies have demonstrated activated CD8+ cells and reduced function of natural killer cells suggesting a host response to an infection that has led to persistent immune disorders. Some of the symptoms of CFS may be due to cytokines produced by this hyperactive immune response to a virus that is still present in the host or that has been eliminate but leaves abnormal immunologic sequelae. These possibilities offer directions for future studies of CFS and therapeutic approaches to this condition.

 

Source: Levy JA. Viral studies of chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S117-20. http://www.ncbi.nlm.nih.gov/pubmed/8148437

 

The chronic fatigue syndrome

Abstract:

CFIDS (chronic fatigue and immune disfunction syndrome) is also known as CFS (chronic fatigue syndrome), CEBV (chronic Epstein-Barr virus), M.E. (myalgic encephalomyelitis), yuppie flu and by other names.

It is a complex illness characterized by incapacitating fatigue (experienced as exhaustion and extremely poor stamina), neurological problems and a constellation of symptoms that can resemble many disorders, including; mononucleosis, multiple sclerosis, fibromyalgia, AIDS-related complex (ARC) and autoimmune diseases such as lupus. These symptoms tend to wax and wane, but any often severely debilitating and may last for many months or years. All sections of the population (including children) are at risk, but women under 45 seem to be most susceptible.

The investigators suggest that CFIDS results from dysfunction of the immune system. The exact nature of this dysfunction is not yet well defined, but it can generally be viewed as an unregulated or overactive state which is responsible for most of the symptoms. There is also evidence of some immune suppression in CFIDS. None of the treatments is consistently satisfactory, but some may be helpful: psychotherapy, physiotherapy, exercise programs, acupunctures, small doses of antidepressants, etc.

 

Source: Artsimovich NG, Chugunov VS, Kornev AV, Ivanova TM, Chugunov AV, Oprishchenko MA. The chronic fatigue syndrome. Zh Nevrol Psikhiatr Im S S Korsakova. 1994;94(5):47-50. [Article in Russian] http://www.ncbi.nlm.nih.gov/pubmed/7900453

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214