好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Interferon beta-1a Treatment Inhibits Th1- and Th17-Cell Responses in Patients with Relapsing-Remitting Multiple Sclerosis
MS and Related Diseases
P05 - (-)
144
BACKGROUND: IFN? has been used as a first line therapy for patients with RRMS over the past 20 years, but its mechanisms of action are still not fully elucidated.
DESIGN/METHODS: Blood samples collected at baseline from untreated healthy controls (HCs) (n=15), and at baseline and 6 months post-IFN?-1a treatment from patients with RRMS (n=23), were used to study the intracellular cytokine production in CD4+ and CD8+ T-cells by flow cytometry analysis, and the expression of inflammatory genes in CD4+ T-cells and monocytes using RT-PCR.
RESULTS: The numbers of IL-22-producing CD4+ and CD8+ T-cells were increased in patients with RRMS, compared to HCs (p=0.039 and p=0.008). Baseline IL-17F gene expression was increased (p=0.026) and IL-4 decreased (p=0.020) in CD4+ T-cells. At 6 months following IFN?-1a treatment, there was a significantly decreased percentage of IL-17F- and IL-22-producing CD4+ T-cells (p=0.016 and p=0.029), and IL-17A- and IL-17F-producing CD8+ T-cells (p=0.031 and p=0.044). IFN?-1a treatment inhibited Th17-cell gene expression, including RORc (p=0.024), IL-17F (p=0.002) and IL-21 (p<0.001), and Th1-cell transcription factor T-bet (p=0.011), while it induced gene expression of Th2-cell transcription factor GATA3 (p<0.001) in CD4+ T-cells. The expression of IL-21R (p=0.046) was increased and IL-27R (p=0.034) decreased in CD4+ T cells. In CD14+ monocytes, IFN?-1a treatment inhibited IL-23 (p<0.05, borderline significant) and TLR9 gene expression (p=0.039), while it induced IL-21R expression (p=0.028).
CONCLUSIONS: IFN?-1a influences multiple cellular responses, including inhibition of the Th1- and Th17-cell responses in patients with RRMS. Th1- and Th17-cell cytokine production and gene expression changes merit further study as biomarkers of the therapeutic efficacy of IFN?-1a.
Authors/Disclosures
Yazhong Tao
PRESENTER 		No disclosure on file
Xin Zhang (UNC At Chapel Hill) No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ) Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo) Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Brooke Hayward, SM, MBA (EMD Serono, Inc.) Brooke Hayward, SM, MBA has received personal compensation for serving as an employee of EMD Serono, Inc., Rockland, MA USA, an affiliate of Merck KGaA, Darmstadt, Germany.
Fernando Dangond, MD, FAAN Dr. Dangond has received personal compensation in the range of $1,000,000+ for serving as a Head, Global Clinical Development (employee for 12 years) with EMD Serono.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center) The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
Silva Markovic-Plese, MD, FAAN (Thomas Jefferson University) Dr. Markovic-Plese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Markovic-Plese has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.