Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome

Abstract:

The psychobehavioral responses and cellular immune function were investigated in healthy people (control, N = 21), adult people with chronic fatigue (fatigue-non-CFS group, N = 24), and patients with chronic fatigue syndrome (CFS, N = 10).

Based on psychobehavioral responses, the fatigue-non-CFS group had low general activity levels (p < .05) and slightly depressive tendencies (p < .01) compared with the control. They had many life event stresses (p < .05) and sleep disturbances (p < .01), and they could not cope appropriately with stresses.

The fatigue-non-CFS group also showed significantly lower natural killer (NK) cell activity (p < .01) and decreased numbers of CD16+ and CD56+ cells (p < .05). Compared with the fatigue-non-CFS group, patients with CFS had higher degrees of physical fatigue (p < .01) and more life event stresses (p < .05).

They had lower general activity levels and social introversion. They were also in a depressive state. NK cell activity and the numbers of CD16+ and CD56+ cells were significantly reduced in patients with CFS (p < .01).

These findings suggest that adult people with chronic fatigue may be in an intermediate state between the healthy control and patients with CFS in terms of psychobehavioral responses and low NK cell activity. We observed three cases in such an intermediate state in whom CFS subsequently developed.

 

Source: Masuda A, Nozoe SI, Matsuyama T, Tanaka H. Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. Psychosom Med. 1994 Nov-Dec;56(6):512-8. http://www.ncbi.nlm.nih.gov/pubmed/7871106

 

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

 

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

 

Infection of natural killer cells by human herpesvirus 6

Abstract:

Natural killer (NK) cells are a functionally defined subset of non-T, non-B lymphocytes of bone marrow origin, which induce lysis of selected target cells, including neoplastic and virus-infected cells. The NK cell function provides an important mechanism of primary defence against viruses in vivo, as demonstrated by the occurrence of multiple herpesvirus infections in patients congenitally lacking NK cells.

Here we show that functionally competent CD3- NK clones can be productively infected by human herpesvirus 6 (HHV-6), a T-lymphotropic DNA virus that may play a role in the acquired immunodeficiency syndrome (AIDS) and in the chronic fatigue syndrome, two disorders associated with a defective NK cell activity.

The infection is cytopathic and induces de novo expression of CD4, an antigen not expressed within the NK lineage, thereby predisposing NK cells to infection by human immunodeficiency virus type 1 (HIV-1).

These results provide evidence that a herpesvirus can directly target and kill NK cells, a potential strategy to suppress the natural anti-viral immunity of the host.

 

Source: Lusso P, Malnati MS, Garzino-Demo A, Crowley RW, Long EO, Gallo RC. Infection of natural killer cells by human herpesvirus 6. Nature. 1993 Apr 1;362(6419):458-62. http://www.ncbi.nlm.nih.gov/pubmed/7681936

 

Lymphocyte phenotype and function in the chronic fatigue syndrome

Abstract:

Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function.

Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry. Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced. The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58). CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B. Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities.

These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions. This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

 

Source: Straus SE, Fritz S, Dale JK, Gould B, Strober W. Lymphocyte phenotype and function in the chronic fatigue syndrome. J Clin Immunol. 1993 Jan;13(1):30-40. http://www.ncbi.nlm.nih.gov/pubmed/8095270

 

A case of chronic fatigue syndrome who showed a beneficial effect by intravenous administration of magnesium sulphate

Abstract:

We have treated a case of chronic fatigue syndrome with atopic diathesis was had suffered general malaise, low grade fever, swelling of the lymph nodes, myalgias and arthralgias for a long time.

A 29-year-old female, who had been treated for atopic dermatitis for 5 years, complained of general malaise in May 1990. She was admitted to the nearest hospital in December 1990 because of low grade fever, swelling of the lymph nodes and an elevation of antinuclear antibody (2520x). She was transferred to our hospital in May 1991.

A diagnosis of collagen disease was not compatible with her condition. In addition to general malaise, fever and lymph node swelling, headache, myalgias, muscle weakness, arthralgias and insomnia were observed, and a diagnosis of chronic fatigue syndrome was made based on the working case definition proposed by Holmes et al.

Although eosinophilia, a high serum level of IgE, and elevation of RAST scores, low NK and ADCC activity, and a reduced level of NK cells in the peripheral blood were detected, serum antibodies to a number of viruses were in the normal range.

Treatments with non-steroid anti-inflammatory drugs, minor tranquilizers and antidepressant drugs were not effective at all. An administration of magnesium sulphate was intravenously performed once a week in order to improve her condition, especially severe general malaise. After about 6-week’s administration of magnesium sulphate, she noticed reduced easy fatigability and an improvement in her impaired daily activities. Finally she was able to leave the hospital in January 1992.(ABSTRACT TRUNCATED AT 250 WORDS)

 

Source: Takahashi H, Imai K, Katanuma A, Sugaya T, Hisano K, Motoya S, Aoki S, Sugiyama T, Yachi. A case of chronic fatigue syndrome who showed a beneficial effect by intravenous administration of magnesium sulphate. Arerugi. 1992 Nov;41(11):1605-10. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1492795

 

Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion.

In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01).

Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05).

 

Source: Goodnick PJ, Sandoval R, Brickman A, Klimas NG. Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome. Biol Psychiatry. 1992 Nov 1;32(9):834-8. http://www.ncbi.nlm.nih.gov/pubmed/1450297

 

Chronic fatigue syndrome–study of 51 cases treated at the Second Tokyo National Hospital

Abstract:

Fifty-one patients with chronic fatigue syndrome (CFS) were studied. Tender points, which are a characteristic clinical feature of fibromyalgia, were found in all but two of the patients at 11.4 points (mean) per patient. IgG antibody titers to EB virus viral capsid antigen were more elevated in the CFS patient group compared to that of the control (p < 0.0015). IgG antibody titers to HHV-6 were not higher in the patient group. NK cell activity was not more decreased in the patient group, whereas, the mean number of NK cells was lower (p < 0.005) in the patient group, when CD57 was used as the NK cell marker. Viral infections and/or disorders in cellular immunity may be important factors in the pathogenesis of CFS.

 

Source: Nishikai M. Chronic fatigue syndrome–study of 51 cases treated at the Second Tokyo National Hospital. Nihon Rinsho. 1992 Nov;50(11):2641-7. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337560

 

Chronic fatigue immune dysfunction syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks.

Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems.

Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS.

 

Source: Uchida A. Chronic fatigue immune dysfunction syndrome. Nihon Rinsho. 1992 Nov;50(11):2625-9. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287238

 

Chronic fatigue syndrome: clinical condition associated with immune activation

Abstract:

There is much conflicting immunological and viral data about the causes of chronic fatigue syndrome (CFS); some findings support the notion that CFS may be due to one or more immune disorders that have resulted from exposure to an infectious agent.

In the present study, flow cytometry and several different recognising T, B, and natural killer (NK) cell populations as well as activation and cell adhesion antigens were used to study 147 individuals with CFS.

Compared with healthy controls, a reduced CD8 suppressor cell population and increased activation markers (CD38, HLA-DR) on CD8 cells were found. The differences were significant (p = 0.01) in patient with major symptoms of the disease. These immunological indices were not observed in 80 healthy individuals, in 22 contacts of CFS patients, or in 43 patients with other diseases.

No correlation of these findings in CFS patients with any known human viruses could be detected by serology. The findings suggest that immune activation is associated with many cases of CFS.

 

Source: Landay AL, Jessop C, Lennette ET, Levy JA. Chronic fatigue syndrome: clinical condition associated with . Lancet. 1991 Sep 21;338(8769):707-12. http://www.ncbi.nlm.nih.gov/pubmed/1679864