{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:19:30Z","timestamp":1793827170560,"version":"4.6.1"},"reference-count":34,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2012,2,16]],"date-time":"2012-02-16T00:00:00Z","timestamp":1329350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>Background: The pathology of neuromyelitis optica (NMO), in contrast to multiple sclerosis, comprises granulocyte infiltrates along extensive lengths of spinal cord, as well as optic nerve. Furthermore, IFN-\u03b2 treatment worsens NMO. We recently found that experimental autoimmune encephalomyelitis (EAE) induced with Th17 cells is exacerbated by IFN-\u03b2, in contrast to disease induced with Th1 where treatment attenuated symptoms.<\/jats:p>\n                  <jats:p>Objective: This study demonstrates the similarities between NMO and Th17 EAE and how neutrophils mediate pathology in Th17 disease.<\/jats:p>\n                  <jats:p>Methods: Levels of blood biomarkers in NMO were assessed by Luminex and ELISA. Effects of IFN-\u03b2 on neutrophils were assessed by culture assays and immunofluorescence. EAE was induced by transfer of myelin-specific Th1 or Th17 cells and treated with Sivelestat sodium hydrate, a neutrophil elastase inhibitor.<\/jats:p>\n                  <jats:p>Results: We show Th17 cytokines, granulocyte chemokines, type 1 interferon and neutrophil elastase are elevated in patients with definitive NMO. In culture, we find that IFN-\u03b2 stimulates neutrophils to release neutrophil elastase. In Th17 EAE, we demonstrate neutrophilic infiltration in the optic nerve and spinal cord which was not present in Th1 EAE. Blockade of neutrophil elastase with Sivelestat had efficacy in Th17 EAE but not Th1 EAE.<\/jats:p>\n                  <jats:p>Conclusions: The similarities between Th17 EAE and NMO indicate that this model represents several aspects of NMO. Neutrophils are critical in the pathologies of both Th17-EAE and NMO, and therefore blockade of neutrophil elastase is a promising target in treating NMO.<\/jats:p>","DOI":"10.1177\/1352458512440060","type":"journal-article","created":{"date-parts":[[2012,2,16]],"date-time":"2012-02-16T22:10:39Z","timestamp":1329430239000},"page":"398-408","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":79,"title":["Protective effect of an elastase inhibitor in a neuromyelitis optica-like disease driven by a peptide of myelin oligodendroglial glycoprotein"],"prefix":"10.1177","volume":"18","author":[{"given":"Katja","family":"Herges","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigit A","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Kolkowitz","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Mandelbaum","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose M","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Maini","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May H","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep","family":"Killestein","sequence":"additional","affiliation":[{"name":"Department of Neurology, VU Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Polman","sequence":"additional","affiliation":[{"name":"Department of Neurology, VU Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra L","family":"Goodyear","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Steinman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Axtell","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, 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