Our data suggest that TRAIL expression is a candidate for pretreatment assessment and might thus be used as a prognostic marker of treatment response to interferon beta in multiple sclerosis.
One of the molecular mechanisms by which IFN-beta exerts its beneficial effect in multiple sclerosis is reduction of MMP-9 expression and increase of its endogenous tissue inhibitor, TIMP-1.
Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was recently shown to degrade interferon beta, one of the drugs used to treat MS. Consequently, the effect of endogenously produced interferon beta or parenterally given interferon beta may be increased by gelatinase B inhibitors.
Interferon-beta is a mainstay therapy of demyelinating diseases, but its effects are incomplete in human multiple sclerosis and several of its animal models.
Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis.
Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple sclerosis patients: a comparison of three methods in a large Australasian cohort.
Interferon-gamma mRNA attenuates its own translation by activating PKR: a molecular basis for the therapeutic effect of interferon-beta in multiple sclerosis.
Some interferon beta (IFNbeta)-treated patients with multiple sclerosis develop antibody-mediated decreased bioactivity with resultant loss of therapeutic effect.
One of these gene clusters was overexpressed in MS versus CN, and particularly enhanced in the clinically most active subgroup of MS. After 46 of the MS patients were treated with interferon-beta (IFNbeta-1b) for two years, IFNbeta responders were clustered in two of the four MS subgroups.
IFNbeta immediately induces a burst of gene expression of proinflammatory chemokines in vitro that have potential relevance to IFNbeta-related early adverse effects in MS patients in vivo.
IFNB-1b should not be administered to demyelinating patients with genetic and clinical characteristics mimicking NMO such as HLA DPB1*0501 allele, longitudinally extensive spinal cord lesion, blindness and CSF pleocytosis even if they have symptomatic cerebral lesions as typically seen in MS.