Interferon-β specifically inhibits interferon-γ-induced class II major histocompatibility complex gene transcription in a human astrocytoma cell line

Ransohoff, Richard M.; Devajyothi, C.; Estes, Melinda L.; Babcock, Gerald T.; Rudick, Richard A.; Frohman, Elliot M.; Barna, Barbara P.

doi:10.1016/0165-5728(91)90054-b

Cited by 86 publications

(37 citation statements)

References 34 publications

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“…MHC class II was not expressed in untreated astrocytes, IFN-␥ strongly up-regulated the molecule, and IFN-␤ alone had no effect. In accordance with previously published data (45)(46)(47), IFN-␤ down-regulated an IFN-␥-mediated MHC class II expression on the astrocytes (Fig. 8A).…”

Section: Ifn-␤ Treatment Does Not Decreased Mhc Class II or Costimulasupporting

confidence: 80%

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Teige

Liu

Issazadeh‐Navikas

2006

The Journal of Immunology

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We have previously investigated the physiological effects of IFN-β on chronic CNS inflammation and shown that IFN-β−/− mice develop a more severe experimental autoimmune encephalomyelitis than their IFN-β+/− littermates. This result was shown to be associated with a higher activation state of the glial cells and a higher T cell cytokine production in the CNS. Because this state suggested a down-regulatory effect of IFN-β on CNS-specific APCs, these results were investigated further. We report that IFN-β pretreatment of astrocytes and microglia (glial cells) indeed down-modulate their capacity to activate autoreactive Th1 cells. First, we investigated the intrinsic ability of glial cells as APCs and report that glial cells prevent autoreactive Th1 cells expansion while maintaining Ag-specific T cell effector functions. However, when the glial cells are treated with IFN-β before coculture with T cells, the effector functions of T cells are impaired as IFN-γ, TNF-α, and NO productions are decreased. Induction of the T cell activation marker, CD25 is also reduced. This suppression of T cell response is cell-cell dependent, but it is not dependent on a decrease in glial expression of MHC class II or costimulatory molecules. We propose that IFN-β might exert its beneficial effects mainly by reducing the Ag-presenting capacity of CNS-specific APCs, which in turn inhibits the effector functions of encephalitogenic T cells. This affect is of importance because activation of encephalitogenic T cells within the CNS is a prerequisite for the development of a chronic progressive CNS inflammation.

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Section: Ifn-␤ Treatment Does Not Decreased Mhc Class II or Costimulasupporting

confidence: 80%

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Teige

Liu

Issazadeh‐Navikas

2006

The Journal of Immunology

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“…Since IFNβ comprises a first-line defense against acute virus infections, the antiviral effects of various therapeutic IFNβ variants may represent a partial explanation for their favorable effects in MS. Another rationale for clinical trials with IFNβs is based on the assumption that cytokines from both immune and non-immune cells play a major role in MS pathophysiology and that IFNβ downregulates proinflammatory Th1 cytokines and upregulates antiinflammatory Th2 cytokines [36,37,38]. However, changes in the profile of Th1/Th2 cytokines during long-term monotherapy with IFNβ-1a or IFNβ-1b have not been investigated in patients with RRMS.…”

Section: Introductionmentioning

confidence: 99%

Effects of Interferon β-1a and Interferon β-1b Monotherapies on Selected Serum Cytokines and Nitrite Levels in Patients with Relapsing-Remitting Multiple Sclerosis: A 3-Year Longitudinal Study

Stępień

Chalimoniuk²,

Lubina-Dąbrowska

et al. 2013

Neuroimmunomodulation

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Objective: Interferon (IFN)β treatment is a mainstay of relapsing-remitting multiple sclerosis (RRMS) immunotherapy. Its efficacy is supposedly a consequence of impaired trafficking of inflammatory cells into the central nervous system and modification of the proinflammatory/antiinflammatory cytokine balance. However, the effects of long-term monotherapy using various IFNβ preparations on cytokine profiles and the relevance of these effects for the therapy outcome have not yet been elucidated. Methods: Changes were compared in serum levels of TNFα, IFNγ, interleukin (IL)-6, IL-10 and nitrite between RRMS patients given 3-year treatment with intramuscular IFNβ-1a (30 μg once a week) or subcutaneous IFNβ-1b (250 μg every other day). Only the data from patients who completed the 3-year study (n = 20 and n = 18, respectively) were analyzed. Results: Three-year IFNβ-1a or IFNβ-1b monotherapy reduced serum nitrite levels by 77 and 71%, respectively, lowered multiple sclerosis relapse annual rate by 70 and 71%, respectively, and significantly and similarly lowered Expanded Disability Status Scale scores in both study groups (by 0.9 on average). The two monotherapies showed little if any effect on cytokine levels and cytokine level ratios after the first year, but exerted diverging effects on these indices later on; the only exception was the IFNγ/IL-6 ratio that showed a monotonous rise in both study groups over the entire study period. Conclusion: During long-term IFNβ monotherapy, the levels of the studied cytokines show no relevance to the course of RRMS and neurological status of patients, whereas there seems to be a link between these clinical indices and the activity of nitric oxide-mediated pathways.

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“…O processo autoimune na EM implica na ativação de células T por um ou mais antígenos da mielina (peptídeos da proteina básica de mielina) apresentadas por moléculas do complexo maior de histocompatibilidade da classe II (MHC II) na superfície de astrócitos, células da microglia e endoteliais no SNC 17,18 O interferon gama é o maior regulador da expressão do MHC II e produz ativação das células macrófagas ou gliais na produção do fator de necrose tumoral alfa, que tem efeito citotóxico nos oligodendrócitos [19][20][21] . O mecanismo de ação proposto para o interferon beta é de que este antagoniza a síntese do interferon gama 22 .…”

Section: Discussionunclassified

Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes

Tilbery¹,

Felipe²,

Moreira³

et al. 2000

Arq. Neuro-Psiquiatr.

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RESUMO -Relatamos os resultados de estudo com o interferon beta 1-a em 62 pacientes ambulatoriais com a forma remitente-recorrente da esclerose múltipla durante um ano. Os critérios de inclusão para este tratamento foram de escore do EDSS entre 0 e 5,5 e de pelo menos relato de dois surtos nos dois últimos anos. Administramos 3 milhões de unidades internacionais de interferon beta 1-a três vezes por semana. Os objetivos deste estudo foram verificar o efeito da medicação no número de surtos e avaliar a eficácia da droga na progressão da doença. O índice anual de surtos nos pacientes que não tomaram a medicação foi 1,32 e naqueles medicados 0,63. O escore do EDSS em pacientes não medicados foi 4,7 e naqueles com medicamento 2,0. O interferon beta 1-a foi bem tolerado e 85% dos pacientes completaram um ano de tratamento.PALAVRAS-CHAVE: interferon beta 1-a, esclerose múltipla, tratamento. Interferon beta 1-a in multiple sclerosis: experience of one year in 62 patientsABSTRACT -We report the results of a trial of interferon beta 1-a in 62 ambulatory patients with relapsingremitting multiple sclerosis. Entry criteria included EDSS of 0 to 5.5 and at least two exacerbations in the previous 2 years. The patients received 3 million international units by subcutaneous injections three times a week. The end points were differences in exacerbation rate and treatment effect on disease progression. The annual exacerbation rate for patients that did not take the interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS score in patients that did not take the mediaction was 4.7 and 2.0 for the patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85% of patients completed 1 year treatment.KEY WORDS: interferon beta 1-a, multiple sclerosis, treatment.A esclerose múltipla (EM) é doença inflamatória e desmielinizante do sistema nervoso central. Admite-se que células T, ativadas por autoantígeno ainda não determinado, passam da periferia para o SNC pela barreira hematoencefálica, evento considerado essencial na patogênese da desmielinização 1,2 . Até o início da década passada, dispunhamos apenas de corticóides e imunossupressores para o tratamento de pacientes com EM entretanto, estes medicamentos apresentam resultados pouco eficazes e não evitam a progressão da doença 3,4 . Após os relatos de Jacobs e Munschauer 5 , inúmeros ensaios clínicos com interferon foram realizados até que ,em 1993, o FDA americano aprovou e autorizou seu uso em pacientes portadores da forma remitenterecorrente da EM 6 .

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Interferon-β specifically inhibits interferon-γ-induced class II major histocompatibility complex gene transcription in a human astrocytoma cell line

Cited by 86 publications

References 34 publications

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Effects of Interferon β-1a and Interferon β-1b Monotherapies on Selected Serum Cytokines and Nitrite Levels in Patients with Relapsing-Remitting Multiple Sclerosis: A 3-Year Longitudinal Study

Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes

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