Article
Corticosteroid resistance in a subpopulation of multiple sclerosis patients as measured by ex vivo dexamethasone inhibition of LPS induced IL-6 production.
Section in Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, 36 Convent Drive (MSC 4020), Bethesda, MD 20892-4020, USA.
Journal of Neuroimmunology (impact factor:
2.96).
07/2004;
151(1-2):180-8.
DOI:10.1016/j.jneuroim.2004.02.009
pp.180-8
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity.
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ABSTRACT: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity. Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR) up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay. We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFα) are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC(50) and IC(50) concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day. In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.Journal of Inflammation Research 01/2012; 5:89-97. -
Article: Impact of exposure to war stress on exacerbations of multiple sclerosis.
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ABSTRACT: To assess the relation between stress caused by the perils of rocket attack on civilian centers in northern Israel during the 2006 war between Hezbollah and Israel and multiple sclerosis (MS) exacerbations. Participants were 156 patients with relapsing-remitting MS. We compared the number of relapses during and after the war with similar time periods at the preceding year. Exposure to war events and resulting subjective stress were evaluated by means of structured interviews using questionnaires previously validated. During the 33 days of the war, there were 18 relapses among our patients, compared with 1 to 6 relapses in similar time periods over the 12 months before the war (p < 0.001-0.02). There was no increase in relapse rate during the 3 months that followed the war (p = 0.58). The percentage of patients reporting the experience of intense subjective stress during the hostilities was significantly greater among patients with wartime relapse compared with the rest of the patients (44 vs 20%). The proportion of patients reporting high levels of distress associated with exposure to rocket attacks, displacement from home, and perceived life threat was greater in relapsing patients compared with those in remission (67 vs 42%, p = 0.05; 33 vs 11%, p = 0.02; and 33 vs 15%, p = 0.08, respectively). Our data suggest that civilian exposure to war stress is associated with increased risk for MS relapse. These findings provide insight to stress-related risk factors associated with relapses of MS.Annals of Neurology 07/2008; 64(2):143-8. · 11.09 Impact Factor -
Article: Brain-immune communication psychoneuroimmunology of multiple sclerosis.
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ABSTRACT: The central nervous system (CNS) and the immune system are two extremely complex and highly adaptive systems. In the face of a real or anticipated threat, be it physical (eg, infection) or psychological (eg, psychosocial stress) in nature, the two systems act in concert to provide optimal adaptation to the demanding internal or environmental conditions. During instances of well being, the communication between these two systems is well tuned and balanced. However, a disturbed crosstalk between the CNS and the immune system is thought to play a major role in a wide series of disorders characterized by a hyporesponsive or hyperresponsive immune system. In multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease, an excess of inflammatory processes seems to be a hallmark and there is growing evidence for a disturbed communication between the CNS and the immune system as a crucial pathogenic factor. While the exact mechanisms for these phenomena are still poorly understood, the young discipline of psychoneuroimmunology (PNI), which focuses on the mechanism underlying the brain to immune crosstalk, might offer some insights into the existing pathogenic mechanisms. Findings from the field of PNI might also help to gain a better understanding regarding the origin and course of MS clinical symptoms such as fatigue and depression.Multiple Sclerosis 02/2008; 14(1):6-21. · 4.26 Impact Factor
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Keywords
50%-inhibition
chronic progressive MS
clinical status
corticosteroid resistance
CPMS
Dex
dexamethasone
higher concentrations
IL)-6 production
LPS
multiple sclerosis
prognosis
relapsing-remitting MS
RRMS
vitro assay
vitro LPS
