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Ligands of the peroxisome proliferator\u2010activated receptor (PPAR) exert anti\u2010inflammatory effects on glial cells, reduce proliferation and activation of T cells, and induce myelin gene expression. We demonstrate in two models of EAE that orally administered PPAR\u03b3 ligand pioglitazone reduced the incidence and severity of monophasic, chronic disease in C57BL\/6 mice immunized with myelin oligodendrocyte glycoprotein peptide and of relapsing disease in B10.Pl mice immunized with myelin basic protein. Pioglitazone also reduced clinical signs when it was provided after disease onset. Clinical symptoms were reduced by two other PPAR\u03b3 agonists, suggesting a role for PPAR\u03b3 activation in protective effects. The suppression of clinical signs was paralleled by decreased lymphocyte infiltration, lessened demyelination, reduced chemokine and cytokine expression, and increased inhibitor of kappa B (IkB) expression in the brain. Pioglitazone also reduced the antigen\u2010dependent interferon\u2010\u03b3 production from EAE\u2010derived T cells. These results suggest that orally administered PPAR\u03b3 agonists could provide therapeutic benefit in demyelinating disease.<\/jats:p>","DOI":"10.1002\/ana.10206","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:29:46Z","timestamp":1030318186000},"page":"694-702","source":"Crossref","is-referenced-by-count":245,"title":["Peroxisome proliferator\u2010activated receptor\u2010\u03b3 agonists prevent experimental autoimmune encephalomyelitis"],"prefix":"10.1002","volume":"51","author":[{"given":"Douglas L.","family":"Feinstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Galea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy","family":"Gavrilyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia 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