Selective COX-2 inhibitor celecoxib prevents experimental autoimmune encephalomyelitis through COX-2-independent pathway.

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-gamma (IFN-gamma) 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.