Complex immunomodulatory effects of interferon-beta in multiple sclerosis include the upregulation of T helper 1-associated marker genes.
Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper-1 lymphocytes. The putative mechanism of interferon-beta (IFN-beta), 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 cytokines. In the present study, a gene expression analysis of IFN-beta-treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN-beta that are not purely anti-inflammatory. 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. Both markers were significantly upregulated in vitro and in vivo under IFN-beta therapy, supporting that this cytokine exerts complex effects on the immune system. The combination of cDNA microarray and quantitative PCR will expand our knowledge of the immunological effects of such pleiotropic agents as IFN-beta, may provide a key to why certain patients fail to respond, and eventually may influence our view of the disease pathogenesis.
Wandinger
K P
KP
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA.
Stürzebecher
C S
CS
Bielekova
B
B
Detore
G
G
Rosenwald
A
A
Staudt
L M
LM
McFarland
H F
HF
Martin
R
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015415:Biomarkers; C508439:IL12RB2 protein, human; D012333:RNA, Messenger; D019713:Receptors, CCR5; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016899:Interferon-beta