Front Biosci. 2004 May 1;9:1547-55
Ahn J, Feng X, Patel N, Dhawan N, Reder AT.
Department of Neurology, The University of Chicago, Chicago, IL 60637,
USA.
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.