IFN-β1b Induces Transient and Variable Gene Expression in Relapsing-Remitting Multiple Sclerosis Patients Independent of Neutralizing Antibodies or Changes in IFN Receptor RNA Expression

ABSTRACT Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Interferon-β (IFN-β) therapy for MS is hypothesized to cause short-term and long-term changes in gene expression that shift the inflammation from Th1 to Th2. In vivo gene induction to define kinetics of response to IFN-β therapy in a large cohort of MS patients is described. Differential gene expression in peripheral blood mononuclear cells (PBMCs) obtained from relapsing-remitting MS patients (RRMS) was assessed using high content microarrays. Rapid onset of gene expression appeared within 4 h of subcutaneous IFN-β administration, returning to baseline levels at 42 h in clinically stable RRMS. IFN-β therapy in vivo rapidly but transiently induced strong upregulation of genes mediating immune modulation, IFN signaling, and antiviral responses. RT-PCR showed significant patient-to-patient variation in the magnitude of expression of multiple genes, especially for IFN-β-inducible genes, such as MxA, IRF7, and CCL...