More MS news articles for Oct 2001

Complex immunomodulatory effects of interferon-b in multiple sclerosis include the upregulation of T helper 1-associated marker genes

http://www3.interscience.wiley.com/cgi-bin/abstract/84502862/START

Annals of Neurology
Volume 50, Issue 3, 2001. Pages: 349-357
Published Online: 27 Jun 2001
Klaus-Peter Wandinger, MD 1, Claus-Steffen Stürzebecher, MD 1, Bibiana Bielekova, MD 1, Greg Detore 1, Andreas Rosenwald, MD 2, Louis M. Staudt, MD, PhD 2, Henry F. McFarland, MD 1, Roland Martin, MD 1 *
1 Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Cancer Institute, National Institutes of Health, Bethesda, MD
2 Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD

Abstract

Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper-1 lymphocytes.

The putative mechanism of interferon-b (IFN-b), an approved treatment for MS, includes the inhibition of T-cell proliferation, blocking of blood-brain-barrier opening and T-cell transmigration into the brain via interference with cell adhesion, and the upregulation of anti-inflammatory (TH2) cytokines.

In the present study, a gene expression analysis of IFN-b-treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN- that are not purely anti-inflammatory.

Specifically, we addressed the effect of IFN-b on T helper-1 differentiation- or lineage markers such as the IL-12 receptor b2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS.

Both markers were significantly upregulated in vitro and in vivo under IFN-b therapy, supporting that this cytokine exerts complex effects on the immune system.

The combination of cDNA microarray and quantitative polymerase chain reaction will expand our knowledge of the immunological effects of such pleiotropic agents as IFN-b, may provide a key to why certain patients fail to respond, and eventually influence our view of the disease pathogenesis.

Funded by:

Deutsche Forschungsgemeinschaft; Grant Number: Wa 1343/1-1
Mildred Scheel Stiftung
NIH

Contact:

email: Roland Martin (martinr@ninds.nih.gov)

*Correspondence to Roland Martin, Neuroimmunology Branch, NINDS, National Institutes of Health, Bldg. 10 Room 5B-16, 10 Center Dr., MSC 1400, Bethesda, MD 20892-1400