Tag: cytokines

Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition.

METHODS: Assays for soluble interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination.

RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01).

CONCLUSION: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CFS and CF.

 

Source: Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol. 1997 Feb;24(2):372-6. http://www.ncbi.nlm.nih.gov/pubmed/9034999

 

Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome

Abstract:

It has been suggested that cytokines play a role in certain clinical manifestations of chronic fatigue syndrome (CFS). In this study adherent (monocytes) and non-adherent (lymphocytes) mononuclear cells were stimulated in the presence or absence of phytohemagglutinin (PHA) or lipopolysaccharide (LPS), respectively, and supernatants were assayed for IL-6, TNF-alpha, and IL-10 by ELISA. IL-6 was also measured at the mRNA level by polymerase chain reaction.

The levels of spontaneously (unstimulated) produced TNF-alpha by non-adherent lymphocytes and spontaneously produced IL-6 by both adherent monocytes and non-adherent lymphocytes were significantly increased as compared to simultaneously studied matched controls. The abnormality of IL-6 was also observed at mRNA level.

In contrast, spontaneously produced IL-10 by both adherent and non-adherent cells and by PHA-activated non-adherent cells were decreased. This preliminary study suggests that an aberrant production of cytokines in CFS may play a role in the pathogenesis and in some of the clinical manifestations of CFS.

 

Source: Gupta S, Aggarwal S, See D, Starr A. Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):149-56. http://www.ncbi.nlm.nih.gov/pubmed/9201656

 

Gender differences in host defense mechanisms

Abstract:

Extensive studies in both humans and animals have shown that females express enhanced levels of immunoreactivity compared to males. Whereas this provides females with increased resistance to many types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on gender-related differences in non-specific host defense mechanisms with a particular emphasis on monocyte/macrophage function and a primary product of monocytes: interleukin-1 (IL-1). Immunomodulatory cytokines such as IL-1 are influenced by gender-sensitive hormones, and reciprocally, these cytokines influence gender-specific hormones and tissues. Patients with chronic fatigue syndrome (CFS) are predominantly women, therefore it may be useful to look toward gender-specific differences in immune function to find a key for this poorly understood syndrome.

 

Source: Cannon JG, St Pierre BA. Gender differences in host defense mechanisms. J Psychiatr Res. 1997 Jan-Feb;31(1):99-113. http://www.ncbi.nlm.nih.gov/pubmed/9201652

 

Immune responses associated with chronic fatigue syndrome: a case-control study

Abstract:

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies.

In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population.

However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen

 

Source: Mawle AC, Nisenbaum R, Dobbins JG, Gary HE Jr, Stewart JA, Reyes M, Steele L, Schmid DS, Reeves WC. Immune responses associated with chronic fatigue syndrome: a case-control study. J Infect Dis. 1997 Jan;175(1):136-41. http://jid.oxfordjournals.org/content/175/1/136.long (Full article)

 

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Abstract:

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group.

PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti.

RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar.

CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Comment in: Etiology of chronic fatigue syndrome. [Am J Med. 1997]

 

Source: MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996 May;100(5):548-54. http://www.ncbi.nlm.nih.gov/pubmed/8644768

 

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome

Abstract:

Whether immunologic abnormalities correlate with fatigue severity and functional impairment in chronic fatigue syndrome (CFS) was investigated. Blood mononuclear cells were immunophenotyped and circulating ex vivo-produced cytokines were measured in 76 CFS patients and 69 healthy matched controls. Expression of CD11b on CD8 cells was significantly decreased in CFS patients. However, the previously reported increased expression of CD38 and HLA-DR was not confirmed. There was no obvious difference in apoptosis in leukocyte cultures, circulating cytokines, and ex vivo production of interleukin (IL)-1 alpha and IL-1 receptor antagonist. Endotoxin-stimulated ex vivo production of tumor necrosis factor-alpha and IL-beta was significantly lower in CFS. The immunologic test results did not correlate with fatigue severity or psychologic well-being was measured by Checklist Individual Strength, Beck Depression Inventory, and Sickness Impact Profile. Thus, these immunologic tests cannot be used as diagnostic tools in individual CFS patients.

 

Source: Swanink CM, Vercoulen JH, Galama JM, Roos MT, Meyaard L, van der Ven-Jongekrijg J, de Nijs R, Bleijenberg G, Fennis JF, Miedema F, van der Meer JW. Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome. J Infect Dis. 1996 Feb;173(2):460-3. http://jid.oxfordjournals.org/content/173/2/460.long (Full article)

 

Are cytokines associated with neuropsychiatric syndromes in humans?

Abstract:

Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals.

In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS).

Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illness, systemic autoimmune diseases and chronic fatigue syndrome).

Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed.

We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.

 

Source: Hickie I, Lloyd A. Are cytokines associated with neuropsychiatric syndromes in humans? Int J Immunopharmacol. 1995 Aug;17(8):677-83. http://www.ncbi.nlm.nih.gov/pubmed/8847162

 

Chronic fatigue syndrome–a controlled cross-sectional study

Abstract:

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals.

Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range.

All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Comment in: [Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. Chronic fatigue syndrome–a controlled cross-sectional study. Ugeskr Laeger. 1994 Nov 14;156(46):6836-40. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839498

 

Current studies on the neurobiology of chronic fatigue syndrome

Abstract:

Cytokines are soluble mediators which are released by activated immune cells during infection and inflammation. The possibility that fatigue is mediated by the effects of cytokines on the central nervous system is supported by several converging lines of evidence: 1) infusions of cytokines to immunocompromised patients induce flu-like symptoms including fatigue and malaise; 2) peripheral and central injection of cytokines to laboratory rodents induce sickness behaviour; 3) symptoms of sickness behaviour occurring during experimental infections can be abrogated by administration of anti-cytokine treatments; 4) although many pitfalls in the detection of cytokines still exist, patients afflicted with the chronic fatigue syndrome have been found in some studies to display instances of excessive production of cytokines.

Experimental studies have confirmed that cytokines are interpreted by the brain as internal signals for sickness. Furthermore, there is evidence that sickness is a motivation which reorganizes the organism’s priorities in face of this particular threat which is represented by infectious pathogens. The elucidation of the mechanisms that are involved in these effects and in particular, the role of the cytokines which are produced in the brain in response to peripheral immune stimuli and to stressors, should give new insight on the way sickness and recovery processes are organized in the brain.

 

Source: Dantzer R. Current studies on the neurobiology of chronic fatigue syndrome. Encephale. 1994 Nov;20 Spec No 3:597-602. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843056

Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression

Chronic fatigue syndrome is characterised by debilitating severe fatigue persisting for more than six months. Furthermore, it is associated with physical symptoms, such as mild fever, sore throat, arthralgia, and myalgia, as well as psychological symptoms such as headache, insomnia, depressive state, and neuropsychiatric symptoms. It has often been claimed that the onset of chronic fatigue syndrome follows an infection or infection-like illness; hence a certain microorganism(s) or virus may cause it. Another possible candidate for inducing chronic fatigue syndrome is cellular or humoral immune dysfunction, which has been found in patients with the disease. There is controversy also as to whether or not chronic fatigue syndrome and major depression (mood disorder) represent different entities.

Mild fever, pharyngitis, and lymphadenopathy, which are suggestive of the existence of inflammation, are often associated with chronic fatigue syndrome, but the peripheral leucocyte count, erythrocyte sedimentation rate, and C-reactive protein concentration are usually normal in patients with chronic fatigue syndrome. Hence, it is possible that certain cytokines may produce the symptoms in patients with chronic fatigue syndrome and, possibly, those with major depression. For example, interferon is known to cause fever, fatigue, and psychoneurological abnormalities. We conducted this study to clarify whether or not 2′,5′-oligoadenylate synthetase (2,5-AS), neopterin, adenosine deaminase, endotoxin, or B-glucan participate in the pathogenesis of chronic fatigue syndrome.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073106/pdf/jnnpsyc00038-0135b.pdf

 

Source: Matsuda J, Gohchi K, Gotoh N. Serum concentrations of 2′,5′-oligoadenylate synthetase, neopterin, and beta-glucan in patients with chronic fatigue syndrome and in patients with major depression. J Neurol Neurosurg Psychiatry. 1994 Aug;57(8):1015-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073106/