Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients

Oliveira, Iara Barreto Neves; Gomes, Rodrigo Saar; Gomides, Larissa Fonseca; Santos, Jéssica Cristina dos; Carneiro, Marcos Alexandre Diniz; Ribeiro‐Dias, Fátima; Diniz, Denise Sisterolli

doi:10.1159/000495787

Cited by 4 publications

(5 citation statements)

References 33 publications

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“…The small sample of veterans with MS was being treated for MS using various disease modifying therapies (DMTs). Various treatment regimens, designed to modulate the immune system, have the potential to alter proinflammatory and anti-inflammatory cytokines (Oliveira et al, 2019;Williamson et al, 2012). The relationship identified between the inflammatory marker cytokines and depression severity in this cross-sectional study may not be true for longitudinal trends.…”

Section: Limitationsmentioning

confidence: 82%

Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

Newland

Basan

Chen

et al. 2021

Biological Research For Nursing

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Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system (CNS), afflicts over one per thousand people in the United States. The pathology of MS typically involves lesions in several regions, including the brain and spinal cord. The manifestation of MS is variable and carries great potential to negatively impact quality of life (QOL). Evidence that inflammatory markers are related to depression in MS is accumulating. However, there are barriers in precisely identifying the biological mechanisms underlying depression and inflammation. Analysis of cytokines provides one promising approach for understanding the mechanisms that may contribute to MS symptoms. Methods: In this pilot study, we measured salivary levels of interleukin (IL)-6, IL-1beta (β), and IL-10 in 24 veterans with MS. Descriptive statistics were reported and Pearson correlation coefficients were obtained between cytokines and depression. Results: The anti-inflammatory cytokine IL-10 was significantly negatively associated with depression in veterans with MS (r = −0.47, p = .024). Conclusion: Cytokines may be useful for elucidating biological mechanisms associated with the depression and a measure for nurses caring for veterans with MS.

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Section: Limitationsmentioning

confidence: 82%

Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

Newland

Basan

Chen

et al. 2021

Biological Research For Nursing

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“…12 It has been demonstrated that activation of TLR2 and TLR4 in dentritic cells or macrophages can indirectly promote leukocyte invasion via the blood-brain barrier and contribute to CNS damage in patients with MS. 13,14 The production of pro-and anti-inflammatory cytokines is induced by stimulation of TLRs. 15,16 The elevated level of TLR2 and TLR4 expression is one form of evidences that supports this thought in patients with MS and EAE, an animal model for MS. [17][18][19] β-D-mannuronic acid (M2000) is a small molecule (patent number: DE/102016113018.4-PCT/ EP2017/067919) with anti-inflammatory properties and low molecular weight, that has not caused any toxicity on bone marrow, kidney, and liver. The hematological, biochemical, and urinalysis findings in the M2000 group did not show any treatment-related adverse effects.…”

mentioning

confidence: 78%

“…It has been demonstrated that activation of TLR2 and TLR4 in dentritic cells or macrophages can indirectly promote leukocyte invasion via the blood‐brain barrier and contribute to CNS damage in patients with MS 13,14 . The production of pro‐ and anti‐inflammatory cytokines is induced by stimulation of TLRs 15,16 . The elevated level of TLR2 and TLR4 expression is one form of evidences that supports this thought in patients with MS and EAE, an animal model for MS 17–19 …”

mentioning

confidence: 89%

The Effects of Mannuronic Acid on IL‐1β, IL‐17A, STAT1, and STAT3 Gene Expressions and TLR2 and TLR4 Molecules in Multiple Sclerosis

Najafi

Saadat

Moghadam

et al. 2022

The Journal of Clinical Pharma

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Multiple sclerosis (MS) is a chronic neurologic disease defined by inflammation and demyelination of the central nervous system that comes with variable degrees of axonal and neuronal damage. The efficacy of β‐D‐mannuronic acid (M2000) as a novel drug with immunosuppressive properties (patented: PCT/EP2017/067920), has been shown in an experimental model of MS. In this study, the effects of M2000 on interleukin (IL)‐1β, IL‐17A, signal transducer and activator of transcription (STAT) 1, and STAT3 gene expressions and Toll‐like receptor 2 (TLR2) and toll‐like receptor 4 (TLR4) molecules in patients with secondary progressive MS were evaluated. In this study, 14 patients with secondary progressive MS and 14 healthy subjects (as control group) were entered from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). The gene expressions of IL‐1β, IL‐17A, STAT1, and STAT3 were assessed at the baseline and then measured after 6 months of therapy with M2000 by using the quantitative real‐time polymerase chain reaction method. Moreover, the expressions of TLR2 and TLR4 molecules on peripheral blood mononuclear cells were evaluated by the flow cytometry method. The gene expressions of IL‐17A, STAT1, and STAT3 in patients with MS decreased after 6 months of therapy with M2000 comparing before treatment. Also, the gene expression of IL‐1β decreased numerically after 6 months. Furthermore, the expressions of TLR2 and TLR4 on PBMCs of the patients declined when compared to baseline. The results of this investigation revealed that M2000 could downregulate IL‐17, STAT1, and STAT3 genes in patients with secondary progressive MS and also reduce the expressions of TLR2 and TLR4 on PBMCs. Moreover, M2000 declined numerically IL‐β gene expression.

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“…The effect of different disease-modifying therapies (DMTs) may be mediated by the modulation of the inflammatory milieu. Treatment with IFN-B in MS is associated with reduced production of TNF compared to untreated patients [ 34 ], decreased RANTES levels [ 28 ], and increased IL-10 release in blood cell cultures [ 35 ]. Treatment with cladribine has been associated with a reduced relapse rate and decreased progression of disability [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment

Bassi

Buttari

Simonelli

et al. 2020

Genes

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In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various proinflammatory cytokines, promoting neuroinflammation and negatively affecting the course of the disease. The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine deaminase (ADA), as evidenced in patients with genetic ADA deficiency and in those treated with cladribine tablets. We investigated in a group of patients with MS the associations of a single nucleotide polymorphism (SNP) of ADA gene with disease characteristics and cerebrospinal fluid (CSF) inflammation. The SNP rs244072 of the ADA gene was determined in 561 patients with MS. Disease characteristics were assessed at the time of diagnosis; furthermore, in 258 patients, proinflammatory and anti-inflammatory molecules were measured in the CSF. We found a significant association between rs244072 and both clinical characteristics and central inflammation. In C-carriers, significantly enhanced disability and increased CSF levels of TNF, IL-5 and RANTES was observed. In addition, lower CSF levels of the anti-inflammatory cytokine IL-10 were found. Finally, the presence of the C allele was associated with a tendency of increased lymphocyte count. In MS patients, ADA SNP rs244072 is associated with CSF inflammation and disability. The selective targeting of the ADA pathway through cladribine tablet therapy could be effective in MS by acting on a pathogenically relevant biological mechanism.

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Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients

Cited by 4 publications

References 33 publications

Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

The Effects of Mannuronic Acid on IL‐1β, IL‐17A, STAT1, and STAT3 Gene Expressions and TLR2 and TLR4 Molecules in Multiple Sclerosis

A Single Nucleotide ADA Genetic Variant Is Associated to Central Inflammation and Clinical Presentation in MS: Implications for Cladribine Treatment

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