RT Journal Article
SR Electronic
T1 Interferon-beta
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP S8
OP S11
DO 10.1212/01.wnl.0000277703.74115.d2
VO 68
IS 24 suppl 4
A1 Clyde E. Markowitz
YR 2007
UL http://n.neurology.org/content/68/24_suppl_4/S8.abstract
AB In patients with multiple sclerosis (MS), activation of immune cells and breakdown of the blood–brain barrier (BBB) lead to demyelination and axon injury. Although repairing damage to neurons is not possible, immunomodulating therapies can reduce the inflammatory processes that lead to demyelination. Interferon-beta (IFN-β) is a polypeptide, normally produced by fibroblasts, that has antiviral and antiproliferative effects. Binding of IFN-β to its receptor induces a complex transcriptional response. In immune cells (the most likely target of IFN-β’s therapeutic effect in MS), IFN-β reduces antigen presentation and T-cell proliferation, alters cytokine and matrix metalloproteinase (MMP) expression, and restores suppressor function. Therapeutic forms of IFN-β can be produced in bacterial expression systems (IFN-β1b) or in mammalian cells (IFN-β1a). These forms have some differences in their amino acid sequence and posttranslational modifications, but the transcriptional response to IFN- β1b and IFN-β1a appears to be similar, if not indistinguishable. However, the biological response and the clinical effect do vary with changes in the dosing frequency of IFN-β. In clinical trials, IFN-β1a IM administered weekly elicits a transient biological response compared to IFN-β1b administered SC every other day or IFN-β1a (administered SC three times per week). Comparative clinical trials suggest that the differences in the biological response are clinically meaningful: more frequent IFN-β administration produces superior clinical responses.