Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The known interaction between the immune system and the hypothalamic-pituitary-adrenal axis led us to explore the interrelation between magnetic resonance imaging findings and the hypothalamic-pituitary-adrenal axis activity in 53 multiple sclerosis patients. The cortisol release induced by the dexamethasone-corticotropin-releasing hormone test was negatively associated with the presence and number of gadolinium-enhancing lesions and positively associated with ventricular size. This finding suggests a protective effect of the hypothalamic- pituitary-adrenal drive on acute lesional inflammation in multiple sclerosis, probably by limiting immune overshoot. In contrast, the nature of the correlation between hypothalamic-pituitary-adrenal hyperdrive and brain atrophy remains to be determined.
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PMID:Activity of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: correlations with gadolinium-enhancing lesions and ventricular volume. 1211 83

Movement disorders associated with multiple sclerosis (MS) are uncommon, except for tremor. We report two patients with relapsing-remitting MS, who developed either dystonia or chorea during clinical exacerbation of their MS. The movement disorders resolved during treatment with adrenocorticotropin hormone (ACTH). Acute exacerbations of MS may be associated with transient movement disorders, which are responsive to ACTH.
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PMID:Transient movement disorders and multiple sclerosis. 1247 1

Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis (MS). During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training. As acute exercise has profound effects on immune and endocrine parameters we studied endocrine and immune response to standardized physical stress in MS within a study of aerobic training. Fifteen MS patients completed an eight-week aerobic training program, 13 patients were part of a wait-control group. Twenty healthy controls were recruited as well. A step-by-step bicycle ergometry was performed to determine individual exertion levels. For the endurance test patients exercised at 60% VO2 max for 30 min. Blood samples were drawn before, directly after and 30 min after completion of the exercise. Heart rate and lactate increased in all groups (p<.0001). We furthermore saw significant increases in endocrine parameters (epinephrine, norepinephrine, ACTH, and beta-endorphin; all p<.0001) in healthy individuals and in MS patients but without a differential effect. Whole-blood stimulated production of IFN-gamma (IFNgamma) was induced similarly in all groups (p<.01). TNF-alpha (TNFalpha) and IL-10 were less inducible in MS patients (trend). From these data we could not demonstrate a proinflammatory immune deviation in response to physical stress in MS. The observed trend of hyporesponsive TNFalpha and IL-10 responses in MS warrants further investigation.
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PMID:Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. 1458 39

In this postmortem study, we investigated the relationship between multiple sclerosis (MS) lesions in the hypothalamus and the state of activity of corticotropin-releasing hormone (CRH)-producing neurons that control the hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions was found in the hypothalamus, of which more than 50% was active, that is, contained activated macrophages. MS patients have increased numbers of CRH-immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of chronic activation of CRH neurons and increased CRH mRNA expression. Active MS lesions correlated with a low number of hyperactive CRH/VP neurons. High human leukocyte antigen (HLA)-DR, -DP, -DQ expression, a measure for macrophage and microglial activation, correlated with low CRH mRNA expression. The nearer the HLA expression was situated to the CRH neurons, the stronger the inhibiting effect, suggesting that activated microglial cells or macrophages suppress these neurons. The more active MS lesions were present in the hypothalamus, the shorter was the disease duration until the moment of death, indicating an unfavorable course of the disease. Thus, MS patients have a chronically activated CRH system, but, in the subgroup of patients with active MS lesions in the hypothalamus, this activation is impaired and the disease course is worse.
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PMID:Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions. 1470 10

The collapse of major histocompatibility complex (MHC) class-I-dependent immune privilege can lead to autoimmune disease or fetal rejection. Pragmatic and instructive models are needed to clarify the as yet obscure controls of MHC class I down-regulation in situ, to dissect the principles of immune privilege generation, maintenance, and collapse as well as to develop more effective strategies for immune privilege restoration. Here, we propose that human scalp hair follicles, which are abundantly available and easily studied, are ideally suited for this purpose: interferon-gamma induces ectopic MHC class I expression in the constitutively MHC class-I-negative hair matrix epithelium of organ-cultured anagen hair bulbs, likely via interferon regulatory factor-1, along with up-regulation of the MHC class I pathway molecules beta(2)microglobulin and transporter associated with antigen processing (TAP-2). In the first report to identify natural immunomodulators capable of down-regulating MHC class I expression in situ in a normal, neuroectoderm-derived human tissue, we show that ectopic MHC class I expression in human anagen hair bulbs can be normalized by treatment with alpha-MSH, IGF-1, or TGF-beta1, all of which are locally generated, as well as by FK506. These agents are promising candidates for immune privilege restoration and for suppressing MHC class I expression where this is clinically desired (eg, in alopecia areata, multiple sclerosis, autoimmune uveitis, mumps orchitis, and fetal or allograft rejection).
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PMID:Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. 1474 67

Peripheral corticotropin-releasing hormone (CRH) is thought to have proinflammatory effects. We used the model of experimental autoimmune encephalomyelitis (EAE) to study the role of CRH in an immune-mediated disease. We showed that CRH-deficient mice are resistant to EAE, with a decrease in clinical score as well as decreased cellular infiltration in the CNS. Furthermore, Ag-specific responses of primed T cells as well as anti-CD3/anti-CD28 TCR costimulation were decreased in crh(-/-) mice with decreased production of Th1 cytokines and increased production of Th2 cytokines. Wild-type mice treated in vivo with a CRH antagonist showed a decrease in IFN-gamma production by primed T cells in vitro. This effect of CRH is independent of its ability to increase corticosterone production, because adrenalectomized wild-type mice had similar disease course and severity as control mice. We found that IkappaBalpha phosphorylation induced by TCR cross-linking was decreased in crh(-/-) T cells. We conclude that peripheral CRH exerts a proinflammatory effect in EAE with a selective increase in Th1-type responses. These findings have implications for the treatment of Th1-mediated diseases such as multiple sclerosis.
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PMID:Corticotropin-releasing hormone contributes to the peripheral inflammatory response in experimental autoimmune encephalomyelitis. 1584 39

We review the evidence indicating a possible beneficial role for UVR on three Th1-mediated autoimmune diseases: multiple sclerosis, type 1 diabetes and rheumatoid arthritis in relation to recent developments in photoimmunology. Recent work suggests that UVR exposure may be one factor that can attenuate the autoimmune activity leading to these three diseases through several pathways involving UVB and UVA irradiation, UVR-derived vitamin D synthesis and other routes such as alpha-melanocyte-stimulating hormone, calcitonin gene related peptide and melatonin. Ecological features, particularly a gradient of increasing prevalence of multiple sclerosis and type 1 diabetes with higher latitude, provide some support for a beneficial role of UVR. Analytical studies provide additional support, particularly as low vitamin D has been prospectively associated with disease onset for all three diseases, but are not definitive. Randomized controlled trial data are required. Further, we discuss how associated genetic studies may assist the accumulation of evidence with regard to the possible causal role of low UVR exposure and/or low vitamin D status in the development of these diseases.
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PMID:UVR, vitamin D and three autoimmune diseases--multiple sclerosis, type 1 diabetes, rheumatoid arthritis. 1597 32

Increased blood-brain-barrier (BBB) permeability precedes any clinical or pathologic signs and is critical in the pathogenesis of multiple sclerosis (MS) and brain metastases. CD4+ TH1 cells mediate demyelination in MS, but how they get sensitized and enter the brain to induce brain inflammation remains obscure. TH2 cytokines associated with allergic disorders have recently been implicated in MS, while genes upregulated in MS plaques include the mast cell-specific tryptase, the IgE receptor (Fc-epsilon-RI) and the histamine-1 receptor. Mast cell specific tryptase is elevated in the CSF of MS patients, induces microvascular leakage and stimulates protease-activated receptors (PAR), leading to widespread inflammation. BBB permeability, MS and brain metastases appear to worsen in response to acute stress that leads to the local release of corticotropin-releasing hormone (CRH), which activates brain mast cells to selectively release IL-6, IL-8 and vascular endothelial growth factor (VEGF). Acute stress increases BBB permeability that is dependent on CRH and mast cells. Acute stress shortens the time of onset of experimental alleric encephalomyelitis (EAE) that does not develop in W/W mast cell deficient or CRH -/- mice. Brain mast cell inhibition and CRHR antagonists offer novel therapeutic possibilities.
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PMID:Corticotropin-releasing hormone and the blood-brain-barrier. 1712 8

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the CNS with an assumed autoimmune-mediated pathogenesis. Stressful life events have been hypothesized as potential triggers of disease exacerbation. Animal studies using experimental autoimmune encephalomyelitis (EAE), as a model for MS, suggest that decreased hypothalamic-pituitary-adrenal (HPA) function may play a role in the increased susceptibility and severity of the disease. Histopathological studies of the hypothalamus point to disturbances in corticotropin-releasing hormone (CRH) regulation as a result of MS lesions in this area. Functional endocrine tests (e.g., the combined Dexamethasone-CRH test) showed a disturbed negative feedback after steroid application in MS patients. Hyper- and hypoactivity of the HPA axis, have been described to be associated with more severe courses. This paper presents an overview of the evidence for a role of HPA dysfunction in EAE and MS based on stress-experimental studies.
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PMID:Stress and hypothalamic-pituitary-adrenal axis function in experimental autoimmune encephalomyelitis and multiple sclerosis - a review. 1760 41

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is the most common crippling neurological disease of young adults in the US. The 2 basic clinical forms of the disease (relapsing and progressive), which can occur singly or in combination, encompass a wide range of clinical severities are usually established between 18 and 35 years of age and can persist an entire lifetime. Life expectancy of 20 years is 85% of normal. Historically, the standard proven and generally accepted clinical treatment of the disease has been corticotropin (ACTH) and methylprednisolone, which benefited clinical relapses but had no effect on clinical disability (the most important factor influencing the lives of individual MS patients) or other aspects of the chronic course of the disease. The most important new development in the treatment of MS has been the introduction of interferon beta into the clinic. Two forms of recombinant interferon beta have been approved by the FDA for use in relapsing MS: interferon beta-1b (IFN-beta-1b) and interferon beta-1a (IFN-beta-1a). The efficacy of IFN-beta-1b in the treatment of relapsing-remitting MS was established first but no effect on physical disability progression was discerned. In contrast, well designed trials of intramuscular IFN-beta-1a (Avonex((R))) 6.0 MIU (30micro) weekly and subcutaneous IFN-alpha-1a (Rebif((R))) 6 MIU (22microg) or 12 MIU (44microg) 3 times weekly produced a significant delay in the time to sustained progression in physical disability, the first MS treatment to exert such a prophylactic effect. Additionally, IFN-beta-1a significantly reduced clinical relapses and acute and chronic brain lesions revealed by MRI examinations. It is currently believed that IFN-beta-1a treatment alters the fundamental course of relapsing MS. The mechanisms of the therapeutic benefit of recombinant interferon betas are incompletely understood but may include augmentation of suppressor T cell function, inhibition of interferon gamma actions, inhibition of T cell activation, or induction of interleukin-10 gene transcription.
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PMID:Appropriate use of interferon beta-1a in multiple sclerosis. 1803 Nov 26


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