Brain Advance Access originally published online on July 10, 2006
Brain 2006 129(8):1984-1992; doi:10.1093/brain/awl170
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Selective COX-2 inhibitor celecoxib prevents experimental autoimmune encephalomyelitis through COX-2-independent pathway
1 Department of Immunology, National Institute of Neuroscience, NCNP Tokyo, Japan 2 Department of Neurology, Kinki University School of Medicine Osaka, Japan 3 Department of Rehabilitation Medicine, Minami-kyoto National Hospital Kyoto, Japan
Correspondence to: Sachiko Miyake, Department of Immunology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan E-mail: miyake{at}ncnp.go.jp
Cyclooxygenase (COX) is a key enzyme of arachidonic acid metabolism and exists as two distinct isoforms. COX-1 is constitutively expressed in most tissues, whereas COX-2 is inducibly expressed at the site of inflammation. Selective inhibitors of COX-2 have been developed and have been used as anti-inflammatory agents. Here, we show that a new-generation COX-2 inhibitor, celecoxib, inhibited experimental autoimmune encephalomyelitis (EAE). Celecoxib, but not other COX-2 inhibitors such as nimesulid, prevented myelin oligodendrocyte glycoprotein (MOG) induced EAE when administrated orally on the day of disease induction. Moreover, celecoxib inhibited EAE in COX-2-deficient mice, indicating that celecoxib inhibited EAE in a COX-2-independent manner. In celecoxib-treated mice, interferon-
(IFN-) production from MOG-specific T cells was reduced and MOG-specific IgG1 was elevated compared with vehicle-treated mice. Infiltration of inflammatory cells into the central nervous system and the expression of adhesion molecules, P-selectin and intercellular adhesion molecule-1 (ICAM-1), and a chemokine, monocyte chemoattractant peptide-1 (MCP-1), were inhibited when mice were treated with celecoxib. These results suggest that celecoxib may be useful as a new additional therapeutic agent for multiple sclerosis.
Key Words: COX-2 inhibitor; celecoxib; experimental autoimmune encephalomyelitis; multiple sclerosis
Abbreviations: CMC, carboxymethylcellulose; COX, cyclooxygenase; EAN, experimental autoimmune neuritis; EAE, experimental autoimmune encephalomyelitis; ELISA, enzyme-linked immunosorbent assay; ICAM-1, intercellular adhesion molecule-1; IFN, interferon; IL, interleukin; LN, lymph node; MCP-1, monocyte chemoattractant peptide-1; MOG, myelin oligodendrocyte glycoprotein; PBS, phosphate-buffered saline
Received February 6, 2006. Revised April 11, 2006. Accepted May 31, 2006.
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