The clinical efficacy of interferon beta (IFN-beta) therapy in reducing exacerbations of relapsing-remitting MS has been related to antagonistic effects on various activities of IFN-gamma, including MHC-II gene induction.
Experiments in which monocytes from normal subjects and MS patients were pre-treated in vitro with methylprednisolone prior to IFN-beta stimulation revealed that induction of HLA-DR was significantly inhibited; in contrast, IFN-beta induced HLA-DR expression was not down-regulated following subsequent in vitro treatment with methylprednisolone.
Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases.
We conclude that long-term cytokine modulation by IFNbeta-1a differs from acute effects and that downregulation of both pro- and anti-inflammatory cytokines, rather than a shift in the cytokine profile, is apparent after 6 months of IFNbeta-1a treatment of MS patients.
Whether the down-regulatory effects on pro-inflammatory and upregulatory effects on anti-inflammatory molecules are a direct result of IFN-beta on the immune system or secondary to clinical stabilization of MS pathology induced by IFN-beta remains to be evaluated.
Thyroid dysfunction and autoimmunity have been reported during type I interferon therapy, namely interferon-alpha for chronic hepatitis or interferon-beta for multiple sclerosis.
We examined whether interferon-beta (IFN-beta) had the ability to regulate the production of chemokines and the expression of their receptors in T cells derived from patients with MS.
Specifically, we addressed the effect of IFN-beta on T helper-1 differentiation- or lineage markers such as the IL-12 receptor beta2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS.
Seizures and extrapyramidal symptoms in a patient with Tourette's syndrome, Asperger's syndrome, and multiple sclerosis treated with interferon beta-1a and clomipramine.
Previously, we have reported the development of a new quantitative-competitive polymerase chain reaction (qc-PCR) method to evaluate interferon-beta (IFNbeta) bioavailability in multiple sclerosis (MS) patients, by measuring mRNA of mixovirus resistance protein A (MxA).
Interferon-beta is thought to provide clinical improvement to multiple sclerosis (MS) patients, in part, through its ability to suppress the generation of IL-12-dependent autoimmune T helper type 1 (Th1) cells by monocyte-derived dendritic cells (DC).
To date, interferon-beta (IFN-beta) is the most effective and reliable therapy in the majority of MS patients, although the mechanisms underlying its therapeutic effects are not fully understood.
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.
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.