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The latter enzymes, as well as TNF\u03b1\u2010converting enzyme and FasL\u2010converting enzyme, can be blocked by matrix metalloproteinase inhibitors (MMPIs). In this study, we show that a potent MMPI was clinically effective in an animal model for MS, experimental autoimmune encephalomyelitis (EAE) in the SJL\/J mouse. Efficacy was remarkable, as indicated by blocking and reversal of acute disease and reduced number of relapses and diminished mean cumulative disease score in chronic relapsing animals. Also, demyelination and glial scarring were significantly decreased in MMPI\u2010treated mice with chronic relapsing EAE, as was central nervous system gene expression for TNF\u03b1 and fasL. It is interesting that expression of the beneficial cytokine interleukin\u20104 (IL\u20104) was increased, and IL\u20104 was expressed on glial cells. The relevance of these compounds for MS was underscored by their ability to specifically inhibit TNF\u03b1 shedding and cytotoxicity of myelin\u2010autoreactive human cytotoxic CD4<jats:sup>+<\/jats:sup> T\u2010cell clones. This is the first report to show a positive effect by MMPIs on chronic relapsing EAE, its central nervous system cytokine profile, and on TNF\u03b1 shedding by human myelin\u2010autoreactive T cells.<\/jats:p>","DOI":"10.1002\/ana.410440110","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:17:07Z","timestamp":1104592627000},"page":"35-46","source":"Crossref","is-referenced-by-count":101,"title":["Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors"],"prefix":"10.1002","volume":"44","author":[{"given":"Wolfgang","family":"Liedtke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Cannella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Mazzaccaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Clements","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen M.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai W.","family":"Wucherpfenning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J. 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