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

Front Biosci. 2004 May 1:9:1547-55. doi: 10.2741/1331.


Interferon-gamma is produced by immune cells before MS exacerbations, and exogenous IFN-gamma treatment causes MS attacks. IFN-beta production, conversely, rises after exacerbations. IFN-beta therapy ameliorates MS, possibly by lowering IFN-gamma secretion and inhibiting responses to IFN-gamma. IFN-gamma effects are regulated by IFN-gamma receptor (IFNGR) expression. IFN-gamma is pro-inflammatory at low IFNGR levels, but induces apoptosis in cells with high IFNGR levels. We studied effects of IFN-beta1a 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-gamma and IL-10, were measured with flow cytometry. Before IFN-beta therapy, intracellular IL-10 was depressed and the IFN-gamma/IL-10 ratio was elevated in MS, particularly during clinical activity. With IFN-beta 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-beta therapy. Expression of the IFNGR-beta chain was low during active untreated disease. After IFN-beta 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-beta therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Female
  • Humans
  • Interferon gamma Receptor
  • Interferon-beta / therapeutic use*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Longitudinal Studies
  • Lymphocyte Count
  • Lymphocytes / immunology
  • Male
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Receptors, Interferon / metabolism*
  • T-Lymphocytes, Helper-Inducer / cytology


  • Receptors, Interferon
  • Interleukin-10
  • Interferon-beta
  • Interferon-gamma