Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development

2003 ◽  
Vol 9 (6) ◽  
pp. 574-578 ◽  
Author(s):  
Akio Suzumura ◽  
Atsushi Ito ◽  
Tetsuya Mizuno
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Strategy ◽  
Phosphodiesterase Inhibitors ◽  
T Helper ◽  
T Helper 1 ◽  
Chain Reaction ◽  
The Central Nervous System ◽  
Antigen Presenting

The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (C NS), were examined to learn how they affect T cell differentiatio n in the C NS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-po lymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional hetero dimer, p70. In addition, the PDEI ibudilast also suppressed interferon-g, but not IL-4 or IL-10, production by myelin oligodendro cyte glycoprotein (MO G)-specific T cells reactivated with MO G in the presence of microglia. Thus, PDEIs may also suppress differentiatio n of T helper 1 (Th1) in the C NS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.

scholarly journals Concerning immune synapses: a spatiotemporal timeline

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 418 ◽  
Author(s):  
Alvaro Ortega-Carrion ◽  
Miguel Vicente-Manzanares
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Helper Cells ◽  
T Helper ◽  
Immune Synapse ◽  
Immune Synapses ◽  
Cognate Antigen ◽  
The Central Nervous System ◽  
Antigen Presenting

The term “immune synapse” was originally coined to highlight the similarities between the synaptic contacts between neurons in the central nervous system and the cognate, antigen-dependent interactions between T cells and antigen-presenting cells. Here, instead of offering a comprehensive molecular catalogue of molecules involved in the establishment, stabilization, function, and resolution of the immune synapse, we follow a spatiotemporal timeline that begins at the initiation of exploratory contacts between the T cell and the antigen-presenting cell and ends with the termination of the contact. We focus on specific aspects that distinguish synapses established by cytotoxic and T helper cells as well as unresolved issues and controversies regarding the formation of this intercellular structure.

First Presentation of an Acquired Demyelinating Syndrome

2017 ◽  
Vol 16 (03) ◽  
pp. 164-170
Author(s):  
Rachel Gottlieb-Smith ◽  
Amy Waldman
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Differential Diagnosis ◽  
Optic Neuritis ◽  
Clinical Features ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
Acute Disseminated Encephalomyelitis ◽  
The Central Nervous System

AbstractAcquired demyelinating syndromes (ADS) present with acute or subacute monofocal or polyfocal neurologic deficits localizing to the central nervous system. The clinical features of distinct ADS have been carefully characterized including optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. These disorders may all be monophasic disorders. Alternatively, optic neuritis, partial transverse myelitis, and acute disseminated encephalomyelitis may be first presentations of a relapsing or polyphasic neuroinflammatory disorder, such as multiple sclerosis or neuromyelitis optica. The clinical features of these disorders and the differential diagnosis are discussed in this article.

MULTIPLE SCLEROSIS IN CHILDREN

PEDIATRICS ◽  
1958 ◽  
Vol 21 (5) ◽  
pp. 703-709
Author(s):  
John C. Gall ◽  
Alvin B. Hayles ◽  
Robert G. Siekert ◽  
Haddow M. Keith
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Mayo Clinic ◽  
Spinal Fluid ◽  
Neurologic Deficits ◽  
The Central Nervous System ◽  
Physical Findings

Forty cases of disease of the central nervous system, characterized by several episodes and disseminated lesions, with onset in childhood and clinically typical of multiple sclerosis, were studied. The disease as it occurs in children does not appear to differ clinically from the disease as observed in adults, in respect to mode of onset, symptoms, physical findings, and changes in the spinal fluid. In the Mayo Clinic series, however, almost twice as many girls as boys were affected. A pediatrician confronted with a child showing evidence of scattered neurologic deficits that remit, particularly a disturbance of vision and co-ordination, should consider the possibility of multiple sclerosis.

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

scholarly journals Diagnosis and treatment of Multiple sclerosis: Brazilian and global overview

2021 ◽  
Author(s):  
Lorrane de Moura Moreira ◽  
Bruna Stefany Alves Françozo ◽  
Bruno Barcelos Pereira ◽  
Camila Almeida Sardinha ◽  
Débora Pimenta Alves ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Research Result ◽  
Motor Action ◽  
The Central Nervous System ◽  
Nutritional Monitoring ◽  
Diagnosis Therapy ◽  
Inflammatory Character

Introduction: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system with a chronic, progressive and inflammatory character. In addition, it presents itself in a heterogeneous way, and can be as an isolated syndrome or as a recurrent remitter, in the first stage, or as progressive, in the second stage. The present work was developed with the objective of determining which is the best form of diagnosis and therapy for multiple sclerosis in Brazil. Methods: The review was performed in PubMed platform, with the descriptors: “multiple sclerosis”, “diagnosis”, “therapy” and “research”. Results: The research result in 148 articles. After a criterious reading and the application of the used criteria, was selected 20 articles. Conclusion: For the diagnosis of this chronic neurological disease, magnetic resonance imaging is used to assess myelination of the different regions of the central nervous system, which is the most suitable for the diagnosis of MS. Μoreover, as a complement, cerebrospinal fluid extraction and blood tests are performed in order to ascertain the concentration of B cells. Regarding therapeutics, this is diversified, including drugs, diets and therapies that stimulate cognition and motor action, such as the use of virtual reality programs and motor images. In relation to drugs, it is of importance that SUS makes natalizumab and ocrelizumab available because they are more efficient and enable users to have a better quality of life. Finally, nutritional monitoring is also suggested to establish a ketogenic or fasting diet in a balanced way

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