Association Between Tumor Necrosis Factor Inhibitor Exposure and Inflammatory Central Nervous System Events

JAMA Neurology, Journal Year: 2020, Volume and Issue: 77(8), P. 937 - 937

Published: May 18, 2020

Tumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood.To evaluate whether associated with demyelinating nondemyelinating CNS in patients an indication use to describe the spectrum of those events.A nested case-control study was conducted using medical records diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; Jacksonville, Florida) January 1, 2003, February 20, 2019. Patients were included if their reported International Statistical Classification Diseases Related Health Problems, Tenth Revision, diagnostic codes US Food Drug Administration-approved disease (ie, arthritis, ankylosing spondylitis, psoriasis psoriatic Crohn disease, ulcerative colitis) interest. matched 1:1 control participants by year birth, type sex.TNF data derived from along inhibitor, cumulative duration exposure, time exposure.The main outcome either (multiple sclerosis other optic neuritis) or (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, vasculitis) event. Association evaluated conditional logistic regression adjusted determine odds ratios (ORs) 95% CIs. Secondary analyses stratification (rheumatoid arthritis non-rheumatoid arthritis).A total 212 individuals included: 106 without events. Of this total, 136 female (64%); median (interquartile range) age onset 52 (43-62) years. Exposure occurred 64 (60%) 42 (40%) increased risk any event (adjusted OR, 3.01; CI, 1.55-5.82; P = .001). These results similar when stratified found predominantly observed 4.82; 1.62-14.36; .005).This that appeared be Whether represents de novo exacerbated pathways requires further research.

Language: Английский

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Imaging Patterns of Toxic and Metabolic Brain Disorders

Radiographics, Journal Year: 2019, Volume and Issue: 39(6), P. 1672 - 1695

Published: Oct. 1, 2019

Toxic and metabolic brain disorders are relatively uncommon diseases that affect the central nervous system, but they important to recognize as can lead catastrophic outcomes if not rapidly properly managed. Imaging plays a key role in determining most probable diagnosis, pointing next steps of investigation, providing prognostic information. The majority cases demonstrate bilateral symmetric involvement structures at imaging, affecting deep gray nuclei, cortical matter, and/or periventricular white some show specific imaging manifestations. When an appropriate clinical situation suggests exogenous or endogenous toxic effects, associated pattern usually indicates restricted group diagnostic possibilities. Nonetheless, literature approached by starting with common causal agents then reaching abnormalities, frequently mixing many different possible Conversely, this article proposes systematic approach address based on patterns encountered practice. Each is suggestive likely differential which more closely resembles real-world scenarios faced radiologists. Basic pathophysiologic concepts regarding cerebral edemas their relation introduced—an topic for overall understanding. presented, main diagnosis each discussed. Online supplemental material available article. ©RSNA, 2019

Language: Английский

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Neuro-Behcet's disease: An update on diagnosis, differential diagnoses, and treatment

Multiple Sclerosis and Related Disorders, Journal Year: 2019, Volume and Issue: 39, P. 101906 - 101906

Published: Dec. 23, 2019

Language: Английский

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TNF Production and Release from Microglia via Extracellular Vesicles: Impact on Brain Functions

Cells, Journal Year: 2020, Volume and Issue: 9(10), P. 2145 - 2145

Published: Sept. 23, 2020

Tumor necrosis factor (TNF) is a pleiotropic cytokine powerfully influencing diverse processes of the central nervous system (CNS) under both physiological and pathological conditions. Here, we analyze current literature describing molecular involved in TNF synthesis release from microglia, resident immune cells CNS main source this brain development neurodegenerative diseases. A special attention has been given to unconventional vesicular pathway TNF, based on emerging role microglia-derived extracellular vesicles (EVs) propagation inflammatory signals mediating cell-to-cell communication. Moreover, describe contribution microglial regulating important functions, including neuroinflammatory response following injury, neuronal circuit formation synaptic plasticity, myelin damage repair. Specifically, available data functions mediated by EVs carrying have scrutinized gain insights possible novel therapeutic strategies targeting foster

Language: Английский

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<p>Remicade^® (infliximab): 20 years of contributions to science and medicine</p>

Biologics, Journal Year: 2019, Volume and Issue: Volume 13, P. 139 - 178

Published: July 1, 2019

On August 24, 1998, Remicade® (infliximab), the first tumor necrosis factor-α (TNF) inhibitor, received its initial marketing approval from US Food and Drug Administration for treatment of Crohn's disease. Subsequently, Remicade was approved in another five adult two pediatric indications both USA across globe. In 20 years since this approval, has made several important contributions to advancement science medicine: 1) clinical trials with established proof concept that targeted therapy can be effective immune-mediated inflammatory diseases; 2) as monoclonal antibody use a chronic condition, helped identifying methods administering large, foreign proteins repeatedly while limiting body's immune response them; 3) need establish Remicade's safety profile required developing new setting standards postmarketing studies, specifically real-world setting, terms approach, size, duration follow-up; 4) study improved our understanding TNF's role system, well pathophysiology range diseases characterized by inflammation; 5) other TNF inhibitors have transformed practices these diseases: remission become realistic goal long-term disability resulting structural damage prevented. This paper reviews how, over course development practice, able make contributions.

Language: Английский

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Neuroprotective effect of linagliptin against cuprizone-induced demyelination and behavioural dysfunction in mice: A pivotal role of AMPK/SIRT1 and JAK2/STAT3/NF-κB signalling pathway modulation

Toxicology and Applied Pharmacology, Journal Year: 2018, Volume and Issue: 352, P. 153 - 161

Published: June 1, 2018

Language: Английский

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Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models

PLoS Biology, Journal Year: 2019, Volume and Issue: 17(6), P. e3000307 - e3000307

Published: June 18, 2019

Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing causes neuroinflammation in the pathway, mechanisms underlying loss–related pathologies are still poorly understood. We examined cortex following noise-induced (NIHL) its role tinnitus rodent models. Our results NIHL associated with elevated expression of proinflammatory cytokines microglial activation—two defining features neuroinflammatory responses—in primary (AI). Genetic knockout tumor necrosis alpha (TNF-α) or pharmacologically blocking TNF-α prevented ameliorated behavioral phenotype mice NIHL. Conversely, infusion into AI resulted signs both wild-type normal hearing. Pharmacological depletion microglia also At synaptic level, frequency miniature excitatory currents (mEPSCs) increased inhibitory (mIPSCs) decreased pyramidal neurons animals This excitatory-to-inhibitory imbalance was completely by pharmacological blockade expression. These implicate as therapeutic target treating other disorders.

Language: Английский

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Re-Examining the Role of TNF in MS Pathogenesis and Therapy

Cells, Journal Year: 2020, Volume and Issue: 9(10), P. 2290 - 2290

Published: Oct. 14, 2020

Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression specific cytokines over the course disease. One major cytokine that has been shown to play pivotal role in MS tumor necrosis factor (TNF). TNF pleiotropic regulating many physiological pathological functions both immune system central nervous (CNS). Convincing evidence from human have demonstrated involvement various hallmarks MS, including dysregulation, demyelination, synaptopathy neuroinflammation. However, due complexity signaling, which includes two-ligands (soluble transmembrane TNF) two receptors, namely receptor type-1 (TNFR1) type-2 (TNFR2), its cell- context-differential expression, targeting an ongoing challenge. This review summarizes on pathophysiological different animal models, with special focus pharmacological treatment aimed at controlling dysregulated signaling this disorder.

Language: Английский

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Adipocyte metabolism is improved by TNF receptor-targeting small RNAs identified from dried nuts

Communications Biology, Journal Year: 2019, Volume and Issue: 2(1)

Published: Aug. 21, 2019

Abstract There is a growing interest in therapeutically targeting the inflammatory response that underlies age-related chronic diseases including obesity and type 2 diabetes. Through integrative small RNA sequencing, we show presence of conserved plant miR159a miR156c dried nuts having high complementarity with mammalian TNF receptor superfamily member 1a (Tnfrsf1a) transcript. We detected both exosome-like nut nanovesicles (NVs) demonstrated such NVs reduce Tnfrsf1a protein dampen TNF-α signaling pathway adipocytes. Synthetic single-stranded microRNAs (ss-miRs) modified 2′- O -methyl group function as miR mimics. In plants, this modification naturally occurs on nearly all RNAs. -methylated ss-miR mimics for decreased markers hypertrophic well TNF-α-treated adipocytes macrophages. effectively suppress inflammation mice, highlighting potential role miR-based, oligonucleotides treating inflammatory-associated metabolic diseases.

Language: Английский

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Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 29, 2021

Autoimmune diseases affect roughly 5-10% of the total population, with women affected more than men. The standard treatment for autoimmune or autoinflammatory had long been immunosuppressive agents until advent immunomodulatory biologic drugs, which aimed at blocking inflammatory mediators, including proinflammatory cytokines. At frontier these drugs are TNF-α blockers. These therapies inhibit action in common such as rheumatoid arthritis, psoriasis, ulcerative colitis, and Crohn’s disease. blockade quickly became “standard care” due to their effectiveness controlling disease decreasing patient’s adverse risk profiles compared broad-spectrum agents. However, anti-TNF-α have limitations, known safety risk, loss therapeutic efficacy drug resistance, lack numerous diseases, multiple sclerosis. next wave truly transformative therapeutics should aspire provide a cure by selectively suppressing pathogenic autoantigen-specific immune responses while leaving rest system intact control infectious malignancies. In this review, we will focus on three main areas active research tolerance. First, tolerogenic vaccines aiming robust, lasting Second, T cell using Tregs (either polyclonal, antigen-specific, genetically engineered express chimeric antigen receptors) establish dominant tolerance cells (engineered delete cells. Third, IL-2 expanding regulatory vivo .

Language: Английский

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