High levels of type 2 cytokine-producing cells in chronic fatigue syndrome

Abstract:

The aetiology of chronic fatigue syndrome (CFS) is not known. However, it has been suggested that CFS may be associated with underlying immune activation resulting in a Th2-type response. We measured intracellular production of interferon (IFN)-gamma and interleukin (IL)-2; type 1 cytokines), IL-4 (type 2) and IL-10 (regulatory) by both polyclonally stimulated and non-stimulated CD4 and CD8 lymphocytes from patients with CFS and control subjects by flow cytometry.

After polyclonal activation we 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. Non-stimulated cultures revealed significantly higher levels of T cells producing IFN-gamma or IL-4 in CFS patients. Concluding, we show evidence for 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.

 

Source: Skowera A, Cleare A, Blair D, Bevis L, Wessely SC, Peakman M. High levels of type 2 cytokine-producing cells in chronic fatigue syndrome. Clin Exp Immunol. 2004 Feb;135(2):294-302. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808936/ (Full article)

 

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement

Abstract:

The aims of this study were to evaluate the serological response to treatment with staphylococcal vaccine in fibromyalgia/chronic fatigue syndrome patients and to explore the relationship between serological response and clinical effect.

Twenty-eight patients, half of whom served as controls, were recruited from a 6-month randomised trial in which repeated administration of the staphylococcal toxoid vaccine Staphypan Berna (Berna Biotech, Switzerland) was tested against placebo. Antibody status against extracellular toxins/enzymes, cell-wall components, and enterotoxins was evaluated at baseline and at endpoint. The clinical response to treatment was recorded in rating scales.

In the group receiving active treatment, significant serological changes were recorded, whereas no significant changes were found in controls. Treatment led to a significantly increased capacity of serum to neutralise alpha-toxin and a significant increase in serum IgG to alpha-toxin and lipase. Furthermore, the increase in these parameters combined paralleled the improvement in clinical outcome. Thus, the greater the serological response, the greater was the clinical effect.

In conclusion, this explorative study has shown that repeated administration of the Staphypan Berna vaccine in patients with fibromyalgia/chronic fatigue syndrome causes a serological response to several staphylococcal antigens, particularly to certain extracellular toxins and enzymes. The results further show that this response is related to the clinical outcome of treatment.

 

Source: Zachrisson O, Colque-Navarro P, Gottfries CG, Regland B, Möllby R. Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement. Eur J Clin Microbiol Infect Dis. 2004 Feb;23(2):98-105. Epub 2004 Jan 20. http://www.ncbi.nlm.nih.gov/pubmed/14735403

 

Influenza vaccination: is it appropriate in chronic fatigue syndrome?

Abstract:

Chronic fatigue syndrome (CFS) is a recognized clinical illness of unknown cause and pathophysiologic mechanisms. Immunizing patients against influenza would seem to be a prudent strategy since infection has been associated with symptom exacerbation. However, patients with CFS have demonstrated variable abnormalities in the immune system, the clinical significance of which is unclear. Anecdotal information has suggested that, due to the etiologic uncertainty surrounding CFS, many patients reject immunization, fearful of untoward effects. This article attempts to clarify the situation by reviewing immunologic findings in CFS and influenza vaccines in current use. Results from a recent survey of perceptions of patients with CFS regarding immunization revealed that 31% felt immunization was neither safe nor beneficial. This opinion was universal in those patients who had never received influenza vaccine. Among patients who had received vaccine and experienced an adverse effect, 26% felt the vaccine was safe and 28% felt it was beneficial. Among those who had received vaccine without an adverse effect, 45% believed the vaccine was safe, and 55% felt it was effective. CFS patients as a group expressed concern that influenza vaccine would alter an already dysfunctional immune system, or worsen CFS symptoms.

Significantly more patients with CFS who had never received influenza vaccine voiced this opinion than did patients who had received immunization for influenza in the past. Contrary to the opinions expressed by the sample, clinical trials in CFS have yet to find that any type of immunization has produced a deleterious effect on symptoms or functioning. Moreover, patients with CFS in a randomized, placebo-controlled, double-blind trial of influenza immunization produced an antibody titer in the protective range to inactivated trivalent influenza vaccine, although the geometric mean titer was slightly blunted compared with healthy vaccinees.

Although patients with CFS in placebo and active groups reported four times the number of post-injection adverse effects of healthy vaccinees, data re-analysis revealed that this finding was related to the overlap of common, post-influenza immunization symptoms and CFS constitutional symptoms. CFS is a poorly understood illness and some patients may believe in causal theories that lead to the rejection of disease prevention strategies such as immunization. However, influenza immunization appears to provide protective antibody levels without worsening CFS symptoms or causing excessive adverse effects. Efforts to motivate patients with CFS to obtain annual influenza immunization should take into account illness perceptions and concentrate on education based on placebo-controlled trials.

 

Source: Sleigh KM, Marra FH, Stiver HG. Influenza vaccination: is it appropriate in chronic fatigue syndrome? Am J Respir Med. 2002;1(1):3-9. http://www.ncbi.nlm.nih.gov/pubmed/14720070

 

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance.

METHODS: Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here.

RESULTS: Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability.

CONCLUSION: This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

Comment in: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. [BMC Health Serv Res. 2005]

 

Source: Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER; International Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2003 Dec 31;3(1):25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC317472/ (Full article)

 

Chronic fatigue syndrome: is there a role for occupational therapy?

Abstract:

Chronic Fatigue Syndrome (CFS) continues to evolve as a disabling phenomenon characterized by debilitating fatigue and consequential components that limit the functional ability of persons afflicted with the disease. A composite review of the current literature addresses a brief history, etiology, legitimacy, incidence and prevalence, prognosis, diagnosis, impact, and treatment of CFS. The primary focus illustrates available treatment strategies that have been incorporated into occupational therapy practice. As a profession that has made contributions to populations with chronic disease and symptoms similar to those suffering from CFS, the use of effective methods should reinforce the need for occupational therapy intervention with this population.

 

Source: Rubal E, Iwanenko W. Chronic fatigue syndrome: is there a role for occupational therapy? Occup Ther Health Care. 2004;18(3):33-45. doi: 10.1080/J003v18n03_03. http://www.ncbi.nlm.nih.gov/pubmed/23927616

 

The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study

Abstract:

OBJECTIVE: To explore the effect of granisetron, a 5-HT3 antagonist, on fatigue and functional impairment in patients with chronic fatigue syndrome (CFS).

METHODS: Five female patients were eligible to receive oral granisetron for one month (1 mg a day for the first two weeks and 2 mg a day for the second two weeks). The patients had to be between 18 and 65 years of age and suffering from CFS according to the CDC criteria. The effect was assessed by pre- and post-testing, using validated instruments designed to assess the different dimensions of CFS. Treatment response was also evaluated by visual analogue scales (VAS) for fatigue. Analysis was based on intention to treat.

RESULTS: Treatment with granisetron resulted in significant improvement in fatigue severity and functional impairment. Activity level showed no significant increase.

CONCLUSION: The promising results of this study have encouraged us to perform a placebo-controlled, double-blind study to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Comment in: Pilot studies: one swallow does not make a summer… [Neth J Med. 2003]

 

Source: The GK, Prins J, Bleijenberg G, van der Meer JW. The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study.  Neth J Med. 2003 Sep;61(9):285-9. http://www.njmonline.nl/getpdf.php?id=16 (Full article)

 

Pilot studies: one swallow does not make a summer…

Abstract:

What should we expect from pilot studies, done in small series of patients? In the literature there are many examples of small studies with very promising results, that in subsequent larger or better controlled studies proved to be much less promising, or even disastrous. In some instances the initial favourable outcome was due to selection bias. In others the use of nonvalidated methods of measuring outcome made the reproducibility of promising observations problematic. However, we have to start somewhere. In ths issue The et al. report favourable results of granisetron treatment in four out of five patients with chronic fatigue syndrome. A prospective, randomised, placebo-controlled, double-blind clinical trial with granisetron in patients with chronic fatigue syndrome is now ongoing.

Comment on: The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study. [Neth J Med. 2003]

 

Source: van Gelder T, Smits P. Pilot studies: one swallow does not make a summer… Neth J Med. 2003 Sep;61(9):270-2. http://www.njmonline.nl/getpdf.php?id=13 (Full article)

 

Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from peripheral blood mononuclear cells of chronic fatigue syndrome patients

Abstract:

Bojungikki-tang (BIT) has been widely used to treat patients suffering from chronic fatigue syndrome (CFS). However, its effect has not been yet investigated experimentally. Based upon the clinical presentation of CFS, we hypothesized that cytokines may play a role in the pathogenesis of the disease. We studied the effect of BIT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients. Bojungikki-tang (1 mg/mL) significantly inhibited LPS-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta1 production by 63.55% +/- 0.19%, 55.06% +/- 0.27%, 48.23% +/- 0.48%, 54.09% +/- 0.76%, respectively (P < 0.05). Bojungikki-tang showed a slightly lower inhibitory effect of LPS-induced Interferon (IFN)-gamma production. These results suggest that BIT may be useful in treating fatigue associated with chronic diseases.

 

Source: Shin HY, Shin CH, Shin TY, Lee EJ, Kim HM. Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from peripheral blood mononuclear cells of chronic fatigue syndrome patients. Immunopharmacol Immunotoxicol. 2003 Nov;25(4):491-501. http://www.ncbi.nlm.nih.gov/pubmed/14686792

 

Medication use by persons with chronic fatigue syndrome: results of a randomized telephone survey in Wichita, Kansas

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities, and a characteristic symptom complex. Patients use a variety of prescribed and self-administered medications, vitamins, and supplements for relief of their symptoms. The objective of this study was to describe utilization of medications and supplements by persons with CFS and non-fatigued individuals representative of the general population of Wichita, Kansas.

METHODS: We used a random-digit dialing telephone survey to identify persons with CFS in the general population of Wichita, Kansas. Subjects who on the basis of telephone interview met the CFS case definition, and randomly selected non-fatigued controls, were invited for a clinic evaluation that included self-reported use of medications and supplements. Sex-adjusted odds ratios and 95% confidence interval were estimated to measure the association between CFS and use of various drug categories.

RESULTS: We clinically evaluated and classified 90 subjects as CFS during the study and also collected clinical data on 63 who never described fatigue. Subjects with CFS reported using 316 different drugs compared to 157 reported by non-fatigued controls. CFS subjects were more likely to use any drug category than controls (p = 0.0009). Pain relievers and vitamins/supplements were the two most common agents listed by both groups. In addition CFS persons were more likely to use pain relievers, hormones, antidepressants, benzodiazepines, gastro-intestinal, and central nervous system medications (Sex-adjusted odds ratios range = 2.97 – 12.78).

CONCLUSION: Although the reasons for increased use of these agents were not elucidated, the data indicated the CFS patients’ need for symptom relief.

 

Source: Jones JF, Nisenbaum R, Reeves WC. Medication use by persons with chronic fatigue syndrome: results of a randomized telephone survey in Wichita, Kansas. Health Qual Life Outcomes. 2003 Dec 2;1:74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC293479/ (Full article)

 

Chronic fatigue syndrome. The patient centred clinical method–a guide for the perplexed

Abstract:

BACKGROUND: Chronic fatigue states are common in general practice and over the past 20 years there has been considerable worldwide consensus developed on the criteria for chronic fatigue syndrome (CFS) also commonly known as myalgic encephalomyelitis (ME). Chronic fatigue syndrome is an illness characterised by the new onset of disabling fatigue, accompanied by cognitive, musculoskeletal and sleep symptoms. There are no specific diagnostic tests or biological markers and the diagnosis is made by ruling out other causes of fatigue. The pathophysiology of CFS is still unclear.

OBJECTIVE: This article discusses the application of the patient centred clinical method to the diagnosis and treatment of CFS.

DISCUSSION: There is no new breakthrough in the diagnosis or management of CFS in spite of much research and controversy. There is considerable evidence that the best place to manage CFS is in primary care under the care of the patient’s own general practitioner, but it has been suggested that doctors feel unable to deal with the problem. The patient centred clinical method offers a constructive guide to management. The author considers that the best hope for sufferers is self management guided by a supportive and helpful health professional, preferably the patient’s own GP.

 

Source: Murdoch JC. Chronic fatigue syndrome. The patient centred clinical method–a guide for the perplexed. Aust Fam Physician. 2003 Nov;32(11):883-7. http://www.ncbi.nlm.nih.gov/pubmed/14650782