Tag: cytokines

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome

Abstract:

OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls.

METHOD: Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test.

RESULTS: CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels.

CONCLUSION: CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha.

 

Source: Gaab J, Rohleder N, Heitz V, Engert V, Schad T, Schürmeyer TH, Ehlert U. Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocrinology. 2005 Feb;30(2):188-98. http://www.ncbi.nlm.nih.gov/pubmed/15471616

 

Effect of Kuibitang on lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells of chronic fatigue syndrome patients

Abstract:

Kuibitang (KBT) is clinically used to treat patients suffering from chronic fatigue syndrome (CFS) in South Korea. However, its effect has not been investigated experimentally. Recent reports have shown that CFS patients display an altered cytokine production. We examined the effect of KBT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients and healthy controls. KBT (1 mg/ml) significantly inhibited LPS-induced tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 production in PBMC of CFS patients. However, LPS-induced interferon-gamma production was significantly increased by KBT (0.01 mg/ml). These results provide evidence of a novel activity of the KBT that regulate cytokines production related with CFS.

 

Source: Shin HY, An NH, Cha YJ, Shin EJ, Shin TY, Baek SH, Kim CH, Lyu YS, Lee EJ, Kim HM. Effect of Kuibitang on lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Ethnopharmacol. 2004 Feb;90(2-3):253-9. http://www.ncbi.nlm.nih.gov/pubmed/15013189

 

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)

 

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

 

Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome

Abstract:

Human parvovirus B19 infection has been associated with various clinical manifestations of a rheumatic nature such as arthritis, fatigue, and chronic fatigue syndrome (CFS), which can persist for years after the acute phase.

The authors have demonstrated recently that acute B19 infection is accompanied by raised circulating levels of IL-1b, IL-6, TNF-a, and IFN-g and that raised circulating levels of TNF-a and IFN-g persist and are accompanied by MCP-1 in those patients who develop CFS.

A resolution of clinical symptoms and cytokine dysregulation after intravenous immunoglobulin (IVIG) therapy, which is the only specific treatment for parvovirus B19 infection, also has been reported. Although CFS may be caused by various microbial and other triggers, that triggered by B19 virus is clinically indistinguishable from idiopathic CFS and exhibits similar cytokine abnormalities and may represent an accessible model for the study of CFS.

 

Source: Kerr JR, Tyrrell DA. Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr Pain Headache Rep. 2003 Oct;7(5):333-41. http://www.ncbi.nlm.nih.gov/pubmed/12946285

 

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome

Abstract:

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS).

METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster.

RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022).

CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Copyright 2003 Wiley-Liss, Inc.

 

Source: Stewart CC, Cookfair DL, Hovey KM, Wende KE, Bell DS, Warner CL. Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome. Cytometry B Clin Cytom. 2003 May;53(1):26-33. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full  (Full article)

 

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

 

Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue

Abstract:

In some patients complaining of chronic fatigue such as those suffering from the chronic fatigue syndrome (CFS), no underlying physical cause can be clearly identified and they typically present a normal thyroid function. Several studies indicate a dysregulation in the type I interferons (IFN-alpha/beta) pathway in CFS resulting in a sustained upregulation of 2(‘),5(‘)-oligoadenylate synthetases (2-5OAS). Likewise, patients treated with IFN-alpha/beta usually complain of severe fatigue as a limiting side effect.

Beside the 2-5OAS, IFN-alpha/beta induce also the expression of three closely related proteins of unknown function termed the 2-5OAS-like (2-5OASL) proteins. The amino acid sequences of the 2-5OASL proteins display 96% identity with the partial sequence of the thyroid receptor interacting protein (TRIP) 14, further contain two typical thyroid hormone receptor (TR) coregulator domains and feature two ubiquitin C-terminal domains.

From these observations, we raise the hypothesis that the 2-5OASL proteins are TRIPs capable of, respectively, repressing TR transactivation and/or signaling the receptor for destruction by the proteasome. Such molecular mechanisms could explain the development of a clinical hypothyroid state in presence of a normal thyroid function.

 

Source: Englebienne P, Verhas M, Herst CV, De Meirleir K. Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue. Med Hypotheses. 2003 Feb;60(2):175-80. http://www.ncbi.nlm.nih.gov/pubmed/12606231

 

Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and chronic fatigue syndrome subjects

Abstract:

The aim of this study was to compare the degree of inflammation present in acute sinusitis, allergic rhinitis, chronic Fatigue Syndrome (CFS), and non-CFS control subjects by measuring cytokine concentrations in nasal lavage fluids. The concentrations of total protein (TP; Lowry assay), nerve growth factor (NGF), tumor necrosis factor (TNF) alpha, and interleukin (IL)-8 were measured by ELISA in nasal lavage fluids from acute sinusitis (n = 13), active allergic rhinitis (n = 16), CFS (n = 95), and non-CFS (n = 89) subjects. CFS and non-CFS groups were subdivided further using allergy skin test and rhinitis score results. Acute sinusitis subjects had significantly higher TP (p = 0.011, ANOVA), TNF-alpha (p = 0.00071), and IL-8 (p = 0.0000027) concentrations and IL-8/TP ratios (p = 0.0030) than the other three patient groups. There were no differences based on skin test or rhinitis score severity within either the CFS or non-CFS groups. The mucopurulent discharge of acute sinusitis contained significantly higher TNF-alpha and IL-8. Neutrophils were a likely source for these cytokines. There were no differences between CFS and non-CFS subjects, making it unlikely that the rhinitis of CFS has an inflammatory component.

 

Source: Repka-Ramirez S, Naranch K, Park YJ, Clauw D, Baraniuk JN. Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and chronic fatigue syndrome subjects. Allergy Asthma Proc. 2002 May-Jun;23(3):185-90. http://www.ncbi.nlm.nih.gov/pubmed/12125506

 

Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions

Abstract:

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

 

Source: Mullington JM, Hinze-Selch D, Pollmächer T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions.  Ann N Y Acad Sci. 2001 Mar;933:201-10. http://www.ncbi.nlm.nih.gov/pubmed/12000021