Mechanisms of action of interferon-? in multiple sclerosis

Arnason, Barry G. W.; Dayal, Amit; Qu, Zhi; Jensen, Mark A.; Genç, Kürşad; Reder, Anthony T.

doi:10.1007/bf00792613

Cited by 69 publications

(22 citation statements)

References 144 publications

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“…Peripheral autoreactive lymphocytes specific to myelin protein play an important role in the immunopathologic events of MS. (1) The disease is also characterized by an imbalance between proinflammatory and antiinflammatory cytokines, either in the periphery or in the CNS, leading to a prevalence of proinflammatory cytokines (interleukin-1 [IL-1], tumor necrosis factor-␣ [TNF-␣], interferon-␥ [IFN-␥]) that directly or indirectly contribute to the damage to neuronic cells. (2,3) It has been shown that IFN-␤ reduces the rate of exacerbations of relapsing-remitting MS (RRSM) (4,5) and magnetic resonance imaging (MRI)-detected lesions in MS. (6) The mechanisms underlying the beneficial effects of IFN-␤ treatment are not completely clarified but are generally attributed to an immunomodulatory mechanism, (7) and include inhibitory effects on lymphocyte proliferation and migration into CNS, (8,9) antigen presentation, (10) and proinflammatory cytokine secretion. (11) In light of the reported (12) synergistic in vitro and in vivo effects of IFN-␤1a with a phosphodiesterase inhibitor, pentoxifylline (PTX), (12) we studied the immunomodulatory effects of IFN-␤1a alone or associated with oral PTX in two groups of RRMS patients.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Effects of IFN-β1a Treatment Alone or Associated with Pentoxifylline in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS)

Visintini

Telera

Cucurachi

et al. 2005

Journal of Interferon & Cytokine Research

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Interferon-beta1a (IFN-beta1a) and pentoxifylline (PTX) are reported to be active in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms are not completely understood. In two groups of RRMS patients, we studied the phenotype of peripheral lymphocytes and the level of several cytokines both in sera and in supernatants of activated peripheral blood mononuclear cells (PBMC) before and after 8 months of therapy with IFN-beta1a alone or associated with PTX. Our data indicate that patients with RRMS, treated with IFN-beta1a, exhibited a significant increase in CD4(+)CD25(++) T suppressor cells, accompanied by a significant decrease in cytotoxic lymphocytes (CD8(+)CD28(-) and natural killer [NK] cells) and IFN-gamma production, which could both contribute to an explanation of the previously described beneficial effects of IFN-beta treatment in MS. The addition of PTX to IFN-beta1a treatment did not modify the immunomodulatory effects obtained with IFN-beta1a alone. Future studies are needed to demonstrate which immunologic parameters correlate with the clinical benefit of IFN-beta1a treatment.

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Section: Introductionmentioning

confidence: 99%

Immunomodulatory Effects of IFN-β1a Treatment Alone or Associated with Pentoxifylline in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS)

Visintini

Telera

Cucurachi

et al. 2005

Journal of Interferon & Cytokine Research

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“…Interferon beta reduces the exacerbation rate in patients with relapsing remitting (RR) MS, decreases disease activity in the brain (measured as the identification of new or enlarging lesions in serial brain magnetic resonance imaging (MRI)), and slows the progression of MS. Interferon beta exerts a large range of effects on the immune system, which can explain its positive effects on MS, including antagonism of the proinflammatory cytokine interferon gamma (17,18), inhibition of the production of chemokines and matrix metalloproteinases (19), and increased production of Interleukin 10 (20).…”

Section: Discussionmentioning

confidence: 99%

“…It is the first therapeutic intervention demonstrated to modify the natural history of MS (reduces the relapse rate, decreases radiological disease activity, and slows progression of MS). Interferon beta has a range of effects on the immune system, which could explain its positive effects on MS (17,18,19,20).…”

Section: Introductionmentioning

confidence: 99%

Higher Serum Uric Acid Levels in Multiple Sclerosis Patients After Longterm Interferon Beta Treatment

Toncev

Vesić

Aleksić

et al. 2017

Serbian Journal of Experimental and Clinical Research

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Interferon beta is a safe and effi cacious treatment for relapsing multiple sclerosis (MS). However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have benefi cial therapeutic eff ects. Th e aim of this study is to investigate serum uric acid levels in MS patients (272,31±78,21 μmol/l vs. 210,17±53,65 μmol/l; p=0,019, SAŽETAK Interferon beta je bezbedan i efi kasan lek kod relapsno-remitentnog tipa multiple skleroze (MS (272,31 ± 78,21 μmol/l vs. 210,17 ± 53,65 μmol/l; p=0,019,. Nismo utvrdili značajnu razliku u nivoima mokraćne kiseline između grupa pacijenata sa terapijom interferon beta-1a pacijenata sa terapijom interferon beta-1b (p=0.98). Naši rezultati pokazuju da se jedan od korisnih efekata terapije interferonom beta kod MS može bazirati na povišenom nivou mokraćne kiseline koji prirodno uklanja peroksinitrit.

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“…Interferon beta-lb -the first long-term effective treatment of 181 relapsing-remitting and secondary progressive multiple sclerosis (MS) Inhibition ofT cell proliferation (16) Reduced adhesion molecule production (but variable serum levels, 18,19,20) antagonism ofyinterreron effects (16) and down-regulation of interreron-y-induced MHC IT expression (21) Closing of blood-brain barrier disruption (22) inhibition of metalloproteases and NO production in vitro (23,24) Inhibition of pro-inflammatory cytokine production and effects of NO production (23)(24)(25), activation of anti-inflammatory mechanisms (increased IL-1 0 (26, 27) TGFI3 (27), …”

Section: Mode Of Actionmentioning

confidence: 99%

Interferon beta-1b — the first long-term effective treatment of relapsing-remitting and secondary progressive multiple sclerosis (MS)

Horowski¹,

Kapp²,

Steinmayr³

et al. 1999

Biopharmaceuticals, an Industrial Perspective

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Abstract:Beta-intetferons like other type I intetferons are produced in response to viral infections by various mammalian cells. These include macrophages, dendritic cells and fibroblasts. Type I intetferons have non-specific antiviral and anti-proliferative effects, as well as a broad spectrum of immunomodulatory activities. On this basis, type I intetferons are used successfully in the treatment of viral infections such as hepatitis C, papilloma and HIV-l virus. They are also used (mostly in combination with other drugs) to treat some forms of cancer, including leukemia. Whilst these effects could be anticipated from the biological function of type I intetferons, it came as a surprise to most when a group of neurologists presented convincing clinical and laboratory evidence of a relevant and important effect of intetferon beta-l b in multiple sclerosis (MS). These effects were first noted with regard to its earlier relapsing-remitting form, which is marked by reversible exacerbation, and subsequently also in secondary progressive MS with its increasing physical and especially motor disability. We describe the development, clinical effects and side effects as well as the mode of action of this new therapeutic approach to MS.

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Mechanisms of action of interferon-? in multiple sclerosis

Cited by 69 publications

References 144 publications

Immunomodulatory Effects of IFN-β1a Treatment Alone or Associated with Pentoxifylline in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS)

Immunomodulatory Effects of IFN-β1a Treatment Alone or Associated with Pentoxifylline in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS)

Higher Serum Uric Acid Levels in Multiple Sclerosis Patients After Longterm Interferon Beta Treatment

Interferon beta-1b — the first long-term effective treatment of relapsing-remitting and secondary progressive multiple sclerosis (MS)

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