'Outside-in' demyelination in MS

Malpass, Katy

doi:10.1038/nrneurol.2011.217

Cited by 16 publications

(11 citation statements)

References 1 publication

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“…Activation of auto-reactive T cells and increased secretion of inflammatory and neurotoxic factors by microglia leads to demyelination in the CNS (Chabot and Yong 2000; Malpass 2012; Steinman 2001) and subsequent disability. EAE is an induced autoimmune disease in mice that mimics a portion of the clinical signs of MS, resulting in inflammatory demyelination of the CNS by encephalitogenic CD4 + T cells specific for CNS autoantigens (Williams et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

et al. 2015

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Clinical improvement during pregnancy in multiple sclerosis (MS) patients suggests that sex hormones exert potent regulatory effects on immune function. Our previous studies demonstrated that estrogen-(17β-estradiol; E2) mediated protection against experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, hinges on the B cells, leading to elevated numbers of IL-10 secreting CD1d hi CD5 + B regulatory cells (B regs ) in wild type mice. Our data show that co-administration of E2 and IL-10 + B cells ameliorates EAE disease severity and limits CNS infiltrating leukocytes in B cell deficient mice. Additionally, treatment with E2 and B regs reduces demyelination and dramatically decreases the proportion of CD11b + CD45 hi activated microglia/macrophages found in the CNS of immunized animals compared to vehicle, E2 or B reg cells alone. Furthermore, mice given E2 and B regs exhibit increased numbers of peripheral programmed death-1 positive CD4 + Foxp3 + regulatory T cells (T regs ) and up-regulation of programmed death receptor-ligand-1 and CD80 expression on monocytes. Our study suggests IL-10 producing B regs have powerful therapeutic potential as an agent against EAE when augmented with E2 treatment.

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Section: Discussionmentioning

confidence: 99%

Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

et al. 2015

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“…It is assumed that a stimulus agent, such as viral infections or other agents, causes the activation of demyelinating and Copyright © 2018, Archives of Neuroscience. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited autoimmune mechanisms for genetically susceptible individuals (14). Symptoms and the clinical process of the illness vary from a benign silent to a disabling progressive form.…”

Section: Introductionmentioning

confidence: 99%

“…Symptoms and the clinical process of the illness vary from a benign silent to a disabling progressive form. Symptoms first occur in Relapsing-Remitting form while they gradually change into permanent neurological symptoms as the illness advances (14).…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Anxiety and Depression with Disability Over Multiple Sclerosis Patients in Rafsanjan, Iran

et al. 2018

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Background: Multiple sclerosis (MS) is one of the most prevalent diseases of the central nervous system and a category of neurological disorders in which myelin covers of nerves in the brain and spinal cord are locally destroyed and inflamed. Depression is the most prevalent psychiatric disorder, and anxiety is also highly prevalent over MS patients. This research is aimed to study the anxiety and depression frequencies over MS patients. Methods: This is a descriptive-sectional research performed on 132 patients diagnosed with MS by a neurologist in Rafsanjan, Iran. The Beck Depression Inventory and the State-Trait Anxiety Inventory (STAI) by Spielbergeret al. were applied to measure the depression and anxiety, respectively. The disability level was also determined using the expanded disability status scale (EDSS), according to clinical visits and patient histories. The data were then analyzed using SPSS17 in both inferential and descriptive statistics. Results: This research was performed on 132 MS patients including 36 males (27.2%) and 96 females (72.8%). The 21 -40 year-old patient group included the largest portion of the research population. The depression and the state-trait anxiety were evaluated in relation to variables such as their age, gender, occupation, marital status, academic level, taken medications, course of treatment, and disability level. Final results indicated that the state-trait anxiety and depression are not significantly related to the abovementioned factors. Conclusions: It can be concluded that although these factors seem to be somehow influential, no significant effects were found, except between state anxiety and gender, and between depression and marital status.

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“…Peripheral inflammation in this case may be a result of a foreign pathogen (virus), autoimmune activation, or a combination of multiple events. Malpass [31] characterized the term "outside-in" based on evidence of cortical inflammation originating in the subarachnoid space in multiple sclerosis patients which transitioned into the white matter [32]. This further strengthens the argument for modulation of the peripheral inflammatory response which is facilitating early multiple sclerosis disease through activation of CD4 T lymphocytes.…”

Section: Inflammation In Multiple Sclerosismentioning

confidence: 72%

Enkephalin Therapy Improves Relapsing-Remitting Multiple Sclerosis

Patel¹,

Zagon²,

Thomas³

et al. 2020

An Overview and Management of Multiple Chronic Conditions

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Multiple sclerosis (MS) is accompanied by decreases in serum endogenous enkephalin/endorphins and alterations in inflammatory cytokines. This retrospective analysis of serum levels was conducted in 53 patients with established relapsing-remitting MS treated with the disease-modifying therapies (DMT) glatiramer acetate, dimethyl fumarate or with the biotherapeutic low dose naltrexone (LDN) to elevate enkephalins, an off-label alternative. Opioid growth factor (OGF), an inhibitory endogenous opioid involved in modulating cellular replication, was measured and correlated to serum β-endorphin, IL-17A and TNFα. Results revealed that MS leads to a significant reduction in OGF levels in subjects on DMTs, but patients on LDN had OGF levels comparable to non-MS controls. Individuals on DMTs had significantly elevated TNFα levels, while IL-17A levels were significantly elevated only in patients taking dimethyl fumarate. A direct correlation was established between OGF and IL17A indicating a potential interaction between the OGF-OGFr axis and pro-inflammatory T-helper cells providing insight into the disease etiology.

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'Outside-in' demyelination in MS

Cited by 16 publications

References 1 publication

Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

Relationship Between Anxiety and Depression with Disability Over Multiple Sclerosis Patients in Rafsanjan, Iran

Enkephalin Therapy Improves Relapsing-Remitting Multiple Sclerosis

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