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J Neuroimmunol. 2008 Mar;195(1-2):116-20. doi: 10.1016/j.jneuroim.2007.12.007. Epub 2008 Feb 14.

IFN-beta-regulated genes show abnormal expression in therapy-naïve relapsing-remitting MS mononuclear cells: gene expression analysis employing all reported protein-protein interactions.

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Department of Computational Biology, Bayer HealthCare Pharmaceuticals, 2600 Hilltop Dr., Richmond, CA 94806, USA.


The molecular mechanism by which interferon beta (IFN-beta) is effective in treating multiple sclerosis is not well understood. Mononuclear cells from therapy-naïve MS patients, IFN-beta-1b-treated MS patients, and healthy controls were analyzed to examine mRNA changes that characterize both the disease and its treatment. The scientific literature was comprehensively searched for all protein-protein interactions. In MS patients who had never been treated with IFN-beta, statistical analysis revealed coordinate changes in mRNA expression for proteins reported in the literature as "regulated by IFN-beta." As a positive control for this approach, samples from a separate MS patient cohort showed significant change of these same genes during in vivo treatment with IFN-beta-1b.The strength of effect observed for regulation by IFN-beta was greater than for IFN-alpha, IFN-gamma (Th1), or IL-4 (Th2). Of the sets we investigated, the most strongly affected by disease was the subset defined by regulation by both IFN-beta and IFN-alpha. Changes in cells from therapy-naïve MS patients thus anticipated the importance of IFN-beta in therapy. These findings are a significant step towards marrying MS disease etiology and IFN-beta mechanism of action at a molecular level.

[Indexed for MEDLINE]

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