IMR Press / FBL / Volume 9 / Issue 2 / DOI: 10.2741/1331

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Abnormal levels of interferon-gamma receptors in active multiple sclerosis are normalized by IFN-β therapy: implications for control of apoptosis

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1 Department of Neurology, The University of Chicago, Chicago, IL 60637, USA
Academic Editor:Alireza Minagar
Front. Biosci. (Landmark Ed) 2004, 9(2), 1547–1555;
Published: 1 May 2004
(This article belongs to the Special Issue Inflammatory disorders of the nervous system)

Interferon-γ is produced by immune cells before MS exacerbations, and exogenous IFN-γ treatment causes MS attacks. IFN-β production, conversely, rises after exacerbations. IFN-β therapy ameliorates MS, possibly by lowering IFN-γ secretion and inhibiting responses to IFN-γ. IFN-γ effects are regulated by IFN-γ receptor (IFNGR) expression. IFN-γ is pro-inflammatory at low IFNGR levels, but induces apoptosis in cells with high IFNGR levels. We studied effects of IFN-β1a therapy on IFNGR expression on PMA/ionomycin-stimulated PBMNC's in 29 patients with active and stable MS. Surface IFNGR-alpha (the binding chain) and IFNGR-beta (signaling chain), as well as intracellular IFN-γ and IL-10, were measured with flow cytometry. Before IFN-β therapy, intracellular IL-10 was depressed and the IFN-γ/IL-10 ratio was elevated in MS, particularly during clinical activity. With IFN-β therapy IL-10 levels increased, suggesting that a Th2 deficit was reversed. The IFNGR-alpha chain was significantly elevated on lymphocytes in stable and active MS patients not receiving IFN-β therapy. Expression of the IFNGR-beta chain was low during active untreated disease. After IFN-β therapy, the IFNGR-beta/alpha ratio increased at 3 months and fell at 12 months. Increased susceptibility to apoptosis with high IFNGR-beta chain expression at 3 months is likely to remove activated T cells during IFN-β therapy.

Nervous system
interferon-γ receptor
multiple sclerosis
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