Interferon β-1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis

Byskosh, P.V.; At, Reder

doi:10.1177/135245859600100502

Cited by 58 publications

(41 citation statements)

References 48 publications

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“…1), as well as the elevated number of HLA-DR ϩ and CD71 ϩ monocytes and lymphocytes (Table I), results from an unknown stimulus for immune cell activation (20,(26)(27)(28). During exacerbations, IL-2, IFN-␥, TNF-␣, and TNF-␤ appear in serum, their respective mRNAs are upregulated in MNC (29)(30)(31)(32), and activated cells increase in the peripheral blood (20,29,33). CD80 ϩ and CD86 ϩ cells, as well as MHC class II ϩ cells (34,35), are also present in active MS plaques.…”

Section: Discussionmentioning

confidence: 99%

Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy.

Genç¹,

Donà²,

Reder³

1997

J. Clin. Invest.

214

141

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Section: Discussionmentioning

confidence: 99%

Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy.

Genç¹,

Donà²,

Reder³

1997

J. Clin. Invest.

214

141

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“…Many assume that the benefit in MS is forged through an IFN-induced Th1 to Th2 shift. Type I IFNs, however, actually enhance Th1 development and function in mice and in MS (Byskosh and Reder 1996). IFN-b corrects the cardinal defect in MS CD8 suppressor function to normal levels (Noronha and others 1992) Many drugs alter immunity.…”

Section: Multiple Drugs Interact With Ifns To Govern Immunitymentioning

confidence: 99%

How Type I Interferons Work in Multiple Sclerosis and Other Diseases: Some Unexpected Mechanisms

Reder

Feng

2014

Journal of Interferon & Cytokine Research

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Type I interferons (IFNs) are important in innate and adaptive immunity. They are used to treat virus infections, cancer, and multiple sclerosis (MS). There are 5 type I IFN families in humans-IFN-a with 13 subtypes, plus IFN-b, e, k, and o. Because their receptor binding affinities vary, these IFNs have different gene induction profiles and quite variable therapeutic effects. IFN-a subtypes may each be specific for certain viruses, but can be neurotoxic. IFN-b induces IFN-a, plus has additional direct effects on target cells. IFN-b was the first therapy approved that could change the course of MS. It has broader specificity than IFN-a, enhances cognition in MS, and may be neuroprotective and can potentially enhance fertility in women. IFNs have tissue-specific and gene-specific roles that are dependent on a balance of the different IFN subtypes, the timing of exposure, and interactions with drugs and environmental factors. The *1,000 genes that are controlled by these IFNs are critical for antiviral immunity and also impact cell proliferation, immune regulation, cytoprotection, and possibly fertility.In multiple sclerosis (MS), cells from the innate and adaptive arms of the immune system cause central nervous system (CNS) inflammation. Adaptive immunity is prominent in the earlier, relapsing/remitting phase of MS (RRMS). Innate immune responses appear to underlie the later secondary progressive (SPMS) phase but are likely to contribute to brain damage at all times. IFN-b therapy for MS prevents and shortens relapses and also reduces new magnetic resonance imaging (MRI) brain lesions, MRI T1 black hole formation, progression, and cognitive loss (Lacy and others 2013). Long-term therapy induces neuroprotectant proteins such as BDNF, NGF, Nrf2, and NCOA7-AS (Croze and others 2013). Five years of IFN-b-1b therapy, begun 8 years after the first symptoms, reduces the death rate by 47% (Goodin and others 2012). The survival benefit is based on less all-cause mortality, but is predominantly from less MS-related death. Its method of action is complex, with dose-dependent changes in different cells and tissues, and variation at different phases of MS. Type I IFNs Differ from Each Other: Implications for Therapy of MS and Other Diseases Different effects of IFN-a and IFN-b on MS, cancer, and virus infectionsMultiple sclerosis. IFN-b is used to treat MS, whereas IFNa is an approved therapy to treat virus infections and cancer. The rationale for these applications is a mix of scientific evidence and tradition. In MS, early small studies showed that moderate to high doses of IFN-b-1b (4-16 M units every other day) reduced relapses (Knobler and others 1993).With human leukocyte IFN-a, however, there were no or minimal benefits (Frith and the AUSTIMS Research Group 1989). Magnetic resonance imaging was still in its infancy and was not performed in this early study. Other small studies of human leukocyte IFN-a, which is composed of multiple subtypes of IFN-a, showed trends for benefit (Knobler and others 1984; Squillacote and ...

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“…The exact mechanism by which IFNβ induces FLSs remains unclear, but IFNβ-mediated changes in cytokine levels, including tumor necrosis factor α, interleukin 6, and IFNγ, may be at least partially responsible. [27][28][29] FLSs are significantly associated with IFNβ-1b and -1a treatment.…”

Section: Disease-modifying Therapies Ifnβ β and Glatiramer Acetatementioning

confidence: 98%

Review: Optimizing Adherence to Multiple Sclerosis Therapies

B¹,

Lucas²,

Kresa-Reahl³

et al. 2008

International Journal of MS Care

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Disease-modifying drugs (DMDs) have transformed the treatment of relapsing-remitting multiple sclerosis (RRMS). Several studies have shown the benefits of long-term treatment in RRMS; however, all multiple sclerosis (MS) therapies are associated with treatment-related tolerability and safety issues that may challenge patient compliance with therapy. Tolerability issues include flulike symptoms and injection-site reactions for interferon β(IFNβ) and lipoatrophy and systemic postinjection reactions for glatiramer acetate (GA). Altered blood cell counts, depression, and elevated liver enzymes, including rare cases of acute liver injury, are safety issues that have been associated with IFNβand, rarely, systemic anaphylactoid reactions with glatiramer acetate. Common tolerability issues associated with natalizumab are hypersensitivity and postinfusion reactions, and mitoxantrone may cause amenorrhea, nausea, and alopecia. Serious safety issues that have limited the use of natalizumab and mitoxantrone as first-line treatments are progressive multifocal leukoencephalopathy for natalizumab and cardiotoxicity and leukemia for mitoxantrone. Although both tolerability and safety issues can affect patient adherence to therapy, numerous strategies are available to manage tolerability and monitor safety issues. Through careful monitoring of treatment-related safety issues, patient education, and tolerability management strategies, treatment nonadherence can be minimized, thereby maximizing the treatment benefits of DMDs.

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Interferon β-1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis

Cited by 58 publications

References 48 publications

Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy.

Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy.

How Type I Interferons Work in Multiple Sclerosis and Other Diseases: Some Unexpected Mechanisms

Review: Optimizing Adherence to Multiple Sclerosis Therapies

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