Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells

Abstract:

It has been proposed that cytokines play a role in the pathogenesis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS). However, different studies have reported conflicting results using enzyme-linked immunosorbent assay or polymerase chain reaction to detect cytokines in these conditions.

In the present study, for the first time, the production of inflammatory [interleukin (IL)-1alpha, IL-6, and TNF-alpha] and anti-inflammatory (IL-10) cytokines by CD14+ and CD14- peripheral blood mononuclear cells (PBMC) from chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) patients and sex- and age-matched normal subjects was investigated at the level of individual cells using the technique of intracellular cytokine staining and flow cytometry. Cultures were carried out in the presence of polymyxin B to inhibit the effect of endotoxins on cytokine production by monocytes.

The mean intensity of fluorescence (MIF) and percentage of CD14+ (monocytes) and CD14- (lymphocytes) cytokine-producing mononuclear cells were comparable in patients and controls in either unstimulated or IFN-gamma-stimulated conditions. Our study indicates that dysregulation of cytokine production by circulating monocytes or non-monocytic cells (lymphocytes) is not a dominant factor in the pathogenesis of CFS/FMS.

 

Source: Amel Kashipaz MR, Swinden D, Todd I, Powell RJ. Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells. Clin Exp Immunol. 2003 May;132(2):360-5. http://www.ncbi.nlm.nih.gov/pubmed/12699429

 

Phantom lymphadenopathy. An association with chronic fatigue syndrome

Comment on: Phantom lymphadenopathy. An association with chronic fatigue syndrome. [Postgrad Med J. 2003]

 

Shee reports an association between chronic fatigue syndrome (CFS) and what he regards as a “phantom lymphadenopathy”.1 However, his failure to observe “true lymphadenopathy” in patients with CFS complaining of swollen lymph glands does not exclude a real, albeit subclinical enlargement of those glands, because he did not compare their dimensions with the ones that were measurable before the appearance of patients’ complaints.

As someone who suffered from CFS and reported on its dramatic resolution thanks to old and new drugs for Addison’s disease,2 I clearly remember that my lymph nodes, just a few days after the abrupt onset of CFS, became mildly painful and began to swell gradually. This slow process of enlargement lasted approximately one month. However, even when my lymph glands stopped swelling further (but continued to be mildly painful), their dimensions were still clinically within normal limits. This may indirectly explain why Shee found that “careful examination did not confirm lymphadenopathy” in CFS patients with “self diagnosed enlarged lymph glands”.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742656/pdf/v079p00185a.pdf

 

Source: Baschetti R. Phantom lymphadenopathy. An association with chronic fatigue syndrome. Postgrad Med J. 2003 Mar;79(929):185. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742656/ (Full article)

 

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS)

Abstract:

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes.

Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia.

The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.

 

Source: Tarello W. Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS). Acta Vet Hung. 2003;51(1):61-72. http://www.ncbi.nlm.nih.gov/pubmed/12688127

 

Immunity Impairment as a Result of Neurohormonal Disorders

Abstract:

An important principle of psychoneuroimmunologic interaction is that immunocytes act as if they were mobile sensitive organs for the central nervous system, producing local and systemic neuropeptides and immunological transmitters with appropriate stimulation. They inform the brain of local damage and mobilize the neuroendocrine system for protection. Their list is long and continues to grow. It includes: somatostatin, vasoactive intestinal peptide, thyroid stimulating hormone, human chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone and other neurotransmitters and hormones, having immunomodulating properties.

This may indicate to close interaction between the immune and neuroendocrine systems, which may be involved into the disease process. A bright example of this may be a disease that has not been closely studied in our country, but is widespread throughout the world. This is the chronic fatigue syndrome, at the base of which lie disturbances of the central nervous, endocrine and immune systems. The idea that the chronic fatigue syndrome is a disturbance of the production of cytokines is related to a number of disturbances in the T system of immunity. It was found back in 1987-1988 that there is an increase in the level of HLA DR and IL-2 receptors and an increase in the ratio CD4/CD8 in patients suffering from this syndrome.

 

Source: Artsimovich NG, Galushina TS, Matvienko MA, Nastoyaschaya NN, Fadeeva TA, Shneidorova MA. Immunity Impairment as a Result of Neurohormonal Disorders. Russ J Immunol. 1999 Dec;4(4):343-345. http://www.ncbi.nlm.nih.gov/pubmed/12687153

 

Primary haemochromatosis: a missed cause of chronic fatigue syndrome?

Abstract:

OBJECTIVE: To determine whether patients previously diagnosed as chronic fatigue syndrome (CFS) actually have primary haemochomatosis (PH).

METHODS: The setting was a Dutch referral centre. Transferrin saturation (TS) was retrospectively evaluated in banked blood samples of 88 patients diagnosed as CFS. Patients with elevated TS values were asked to provide a new overnight fasting blood sample for a second determination of TS and measurement of serum ferritin. The DNA was investigated for mutations in the HFE gene when one of these iron parameters was elevated.

RESULTS: For 19 out of 88 patients with CFS an elevated TS was found. A new blood sample was obtained from 11 of these 19: six had increased TS and two had elevated serum ferritin values. These eight patients were neither C282Y homozygotes nor compound C282Y-H63D heterozygotes. In the eight cases where no new blood samples could be obtained, the TS was > 50% for two of the five men and < 45% for the three female patients.

CONCLUSION: In a group of 88 CFS patients we could exclude PH in all but two of them (prevalence 2.3%; 95% confidence interval 0-5.5%). In our population of CFS patients PH is not more common than in a control population of northern European descent (prevalence 0.25-0.50%).

Comment in: Prevention of organ failure in hereditary haemochromatosis. [Neth J Med. 2002]

 

Source: Swinkels DW, Aalbers N, Elving LD, Bleijenberg G, Swanink CM, van der Meer JW. Primary haemochromatosis: a missed cause of chronic fatigue syndrome? Neth J Med. 2002 Dec;60(11):429-33. http://www.ncbi.nlm.nih.gov/pubmed/12685490

 

Prevention of organ failure in hereditary haemochromatosis

Abstract:

In this editorial the dominant sites of organ manifestations in hereditary haemochromatosis are discussed as well as conditions that can occur as a result of iron-mediated manifestations: liver disease, diabetes mellitus, arthritis, and cardiomyopathy. The incidences of these organ manifestations and their well-known typical symptomatology are mentioned, in order to investigate hereditary haemochromatosis as a possible (missed?) cause of the chronic fatigue syndrome. In particular the limitations of most studies about the prevalence of hereditary haemochromatosis in patients with the chronic fatigue syndrome are clearly summarised.

Comment on: Primary haemochromatosis: a missed cause of chronic fatigue syndrome? [Neth J Med. 2002]

 

Source: Marx JJ. Prevention of organ failure in hereditary haemochromatosis. Neth J Med. 2002 Dec;60(11):419-22. http://www.ncbi.nlm.nih.gov/pubmed/12685487

 

Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome

Abstract:

STUDY OBJECTIVE: To examine whether bronchial hyperresponsiveness (BHR) in patients with chronic fatigue syndrome (CFS) is caused by immune system abnormalities.

DESIGN: Prospective comparative study.

SETTING: A university-based outpatient clinic (Vrije Universiteit; Brussels, Belgium).

PARTICIPANTS: One hundred thirty-seven CFS patients and 27 healthy volunteers.

MEASUREMENTS: Pulmonary function testing, histamine bronchoprovocation test, immunophenotyping, and ribonuclease (RNase) latent determination.

RESULTS: Seventy-three of 137 patients presented with BHR, of whom 64 had normal results of the histamine bronchoprovocation test. No significant differences were found in age or sex characteristics between the groups. There were no differences in the RNase L ratio, total lung capacity, or FEV(1)/FVC ratio between CFS patients with or without BHR. The group of patients in whom BHR was present (BHR+) differs most significantly from the control group with eight differences in the immunophenotype profile in the cell count analysis and seven differences in the percentage distribution profile. The group of patients in whom no BHR was detected (BHR-) only differed from the control subjects in CD25+ count and in the percentage of CD25+ cells. We observed a significant increase in cytotoxic T-cell count and in the percentage of BHR+ patients compared to BHR- patients, which is consistent with the significant reduction in percentage naïve T cells.

CONCLUSIONS: These results refute any association between the cleaving of 80 kd RNase L and BHR. Immunophenotyping of our sample confirmed earlier reports on (chronic) immune activation in patients with CFS, compared to healthy control subjects. BHR+ CFS patients have more evidence of immune activation compared to BHR- patients. Inflammation and the consequent IgE-mediated activation of mast cells and eosinophils, as seen in asthma patients, is unlikely to be responsible for the presence of BHR in patients with CFS.

 

Source: Nijs J, De Becker P, De Meirleir K, Demanet C, Vincken W, Schuermans D, McGregor N. Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome. Chest. 2003 Apr;123(4):998-1007. http://www.ncbi.nlm.nih.gov/pubmed/12684286

 

The relationship between illness attributions and attributional style in Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To examine the relationship between illness attributions and general attributional style in Chronic Fatigue Syndrome (CFS).

METHOD: Participants with CFS answered questions on their explanation for their illness and completed the Attributional Style Questionnaire (parallel form).

RESULTS: Of the participants, 58.3% attributed their illness to predominantly physical factors. A significant relationship was found between the presence of a self-serving attributional style and illness attributions.

CONCLUSION: Illness attributions were associated with an individual’s general attributional style. It is suggested that illness attributions may be less important with regards prognosis than, for example, other variables which influence a person’s general view of the world.

 

Source: Creswell C, Chalder T. The relationship between illness attributions and attributional style in Chronic Fatigue Syndrome. Br J Clin Psychol. 2003 Mar;42(Pt 1):101-4. http://www.ncbi.nlm.nih.gov/pubmed/12675983

 

Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). We have challenged this notion by examining perceived exertion in civilian females with CFS and expressing the data relative to exercise capacity (%[OV0312]O(2max)). The purpose of the present investigation was to further examine RPE during exercise in a unique population of CFS patients, Gulf veterans (GV).

METHODS: Thirty-four GV (N = 15 CFS, 42 +/- 8 yr; N = 19 healthy, 43 +/- 5 yr) performed a maximal exercise test on a cycle ergometer. After a 3-min warm-up, exercise intensity increased by 30 W every minute until exhaustion. RPE were obtained during the last 15 s of each minute using Borg’s CR-10 scale.

RESULTS: With the exception of peak [OV0312]E, there were no significant differences in any peak exercise variables. Repeated measures ANOVA revealed significantly higher RPE at each power output examined (F(1,32) = 16.4, P < 0.001). Group differences in RPE remained significant when analyzed relative to peak [OV0312]O(2) (F(1,32) = 7.2, P = 0.01). Both group main effects and the interaction were eliminated when self-reported fatigue symptoms were controlled for in the analyses. Power functions for RPE as a function of relative oxygen consumption were not different between groups and were significantly greater than a linear value of 1.0 (1.6 +/- 0.3 for both groups, P < 0.02).

CONCLUSIONS: Our results show that RPE are greater in GV with CFS regardless of whether the data were expressed in terms of absolute or relative exercise intensity. However, self-reported fatigue associated with CFS eliminated the group differences. These results suggest that GV with CFS were unique compared with their civilian counterparts. Future research aimed at determining the influence of preexisting fatigue on RPE during exercise is warranted.

 

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):569-74. http://www.ncbi.nlm.nih.gov/pubmed/12673138

 

Perceived exertion in fatiguing illness: civilians with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). However, methodological limitations have rendered this conclusion suspect. The purpose of the present investigation was to examine RPE during exercise in civilians with CFS by comparing subjects at both absolute exercise stage and relative oxygen consumption reference criteria.

METHODS: A sample of 39 civilian females (N = 19 CFS, 34 +/- 7 yr; N = 20 healthy controls, 33 +/- 7 yr) underwent a maximal exercise test on a treadmill. RPE were obtained during the last 15 s of each 3-min stage using Borg’s 6-20 scale.

RESULTS: There were no significant differences in peak [OV0312]O(2), RER, or RPE. However, controls exercised longer (20.0 +/- 1.1 vs 15.9 +/- 1.1 min, P = 0.01, healthy vs CFS) and had higher peak HR (183 +/- 3 vs 174 +/- 2 bpm, P = 0.03, healthy vs CFS). Civilians with CFS reported higher RPE at stages 3 through 5 compared with controls (F(3,111)= 3.6,P = 0.017). Preexercise fatigue ratings were not a significant predictor of perceived exertion during exercise. There were no group differences (F(1,37)= 1.9, P = 0.17) when RPE were expressed relative to peak [OV0312]O(2).

CONCLUSIONS: Our results show that RPE are greater in civilians with CFS when the data are expressed in terms of absolute exercise intensity. However, by examining RPE relative to a common maximum (i.e., peak [OV0312]O(2)) no differences were observed. The findings of the present investigation challenge the notion that RPE are dysregulated in CFS.

 

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: civilians with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):563-8. http://www.ncbi.nlm.nih.gov/pubmed/12673137