Recombinant interferon-beta therapy and neuromuscular disorders

Stübgen, Joerg‐Patrick

doi:10.1016/j.jneuroim.2009.04.015

Cited by 15 publications

(10 citation statements)

References 148 publications

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“…IFN-a can inhibit Ag-specific proliferation and prevent inflammation (2,3), but its direct usage is hampered by proinflammatory properties, for example, as those observed in systemic lupus erythematosus and myositis (4). Although type I IFNs (IFN-a and IFN-b) also show clear antiinflammatory properties (5,6), for example, in multiple sclerosis (7), the way by which type I IFN prevents inflammation remains largely obscure.…”

mentioning

confidence: 99%

“…This 28-d arthritis model consists of a sensitization phase (days [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], in which Ag-specific immunity develops, and an effector phase (days 21-28) triggered by intraarticular Ag rechallenge. To prevent development of arthritis, type I IFN signaling must be activated during sensitization, because the same regimen of IFN-a treatment given at the onset of the effector phase has no protective effect.…”

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confidence: 99%

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IDO1 and TGF-β Mediate Protective Effects of IFN-α in Antigen-Induced Arthritis

Chalise

Pallotta

Narendra

et al. 2016

The Journal of Immunology

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IFN-α prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-β signaling for this anti-inflammatory property of IFN-α. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1−/−, or Ifnar−/− mice, treated or not with IFN-α or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-β, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-β and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC. Proliferation was measured by 3H-thymidine incorporation and TGF-β by RT-PCR and ELISA. WT but not Ido1−/− mice were protected from AIA by IFN-α, and Kyn, the main IDO1 product, also prevented AIA, both in WT and Ifnar−/− mice. Protective treatment with IFN-α increased the expression of IDO1 in pDC during AIA, and Ab-mediated depletion of pDC, either during mBSA sensitization or after triggering of arthritis, completely abrogated the protective effect of IFN-α. IFN-α treatment also increased the enzymatic IDO1 activity (Kyn/tryptophan ratio), which in turn activated production of TGF-β. Neutralization of enzymatic IDO1 activity or TGF-β signaling blocked the protective effect of IFN-α against AIA, but only during sensitization and not after triggering of arthritis. Likewise, inhibition of the IDO1 enzymatic activity in the sensitization phase, but not after triggering of arthritis, subdued the IFN-α–induced inhibition of mBSA-induced proliferation. In conclusion, presence of IFN-α at Ag sensitization activates an IDO1/TGF-β–dependent anti-inflammatory program that upon antigenic rechallenge prevents inflammation via pDC.

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confidence: 99%

mentioning

confidence: 99%

IDO1 and TGF-β Mediate Protective Effects of IFN-α in Antigen-Induced Arthritis

Chalise

Pallotta

Narendra

et al. 2016

The Journal of Immunology

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“…On this background, a spectrum of neuromuscular syndromes has been described during IFNβ therapy [70]. In a small case series, 3 children with relapsing-remitting MS who had responded well to IFNβ therapy developed CIDP within 4 months to 4 years into treatment [71].…”

Section: Interferon Betamentioning

confidence: 99%

Drug-induced dysimmune demyelinating neuropathies

Stübgen

2011

Journal of the Neurological Sciences

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“…For example, IFNα, which is the current therapy for chronic hepatitis C infection, fails to clear HCV titers in half of treated patients (1). The cytokine interferon beta (IFNβ) has limited activity against multiple sclerosis in a large segment of patients (2). Cytokine combination therapy, where two or more cytokine-based medications are simultaneous administered to treat a single disease, has shown promise in multiple medical conditions, such as cancer (3), myocardial infarction (4), and osteoporosis (5).…”

Section: Introductionmentioning

confidence: 99%

Combinatorial Cytokine Code Generates Anti-Viral State in Dendritic Cells

et al. 2014

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The physiological function of the immune system and the response to therapeutic immunomodulators may be sensitive to combinatorial cytokine micro-environments that shape the responses of specific immune cells. Previous work shows that paracrine cytokines released by virus-infected human dendritic cells (DC) can dictate the maturation state of naïve DCs. To understand the effects of paracrine signaling, we systematically studied the effects of combinations cytokines in this complex mixture in generating an anti-viral state. After naïve DCs were exposed to either IFNβ or to paracrine signaling released by DCs infected by Newcastle disease virus (NDV), microarray analysis revealed a large number of genes that were differently regulated by the DC-secreted paracrine signaling. In order to identify the cytokine mechanisms involved, we identified 20 cytokines secreted by NDV infected DCs for which the corresponding receptor gene is expressed in naïve DCs. By exposing cells to all combinations of 19 cytokines (leave-one-out studies), we identified five cytokines (IFNβ, TNFα, IL-1β, TNFSF15, and IL28) as candidates for regulating DC maturation markers. Subsequent experiments identified IFNβ, TNFα, and IL1β as the major contributors to this anti-viral state. This finding was supported by infection studies in vitro, by T-cell activation studies and by in vivo infection studies in mouse. Combination of cytokines can cause response states in DCs that differ from those achieved by the individual cytokines alone. These results suggest that the cytokine microenvironment may act via a combinatorial code to direct the response state of specific immune cells. Further elucidation of this code may provide insight into responses to infection and neoplasia as well as guide the development of combinatorial cytokine immunomodulation for infectious, autoimmune, and immunosurveillance-related diseases.

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Recombinant interferon-beta therapy and neuromuscular disorders

Cited by 15 publications

References 148 publications

IDO1 and TGF-β Mediate Protective Effects of IFN-α in Antigen-Induced Arthritis

IDO1 and TGF-β Mediate Protective Effects of IFN-α in Antigen-Induced Arthritis

Drug-induced dysimmune demyelinating neuropathies

Combinatorial Cytokine Code Generates Anti-Viral State in Dendritic Cells

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