title: Treatment of experimental autoimmune uveoretinitis with peroxisome proliferator-activated receptor α agonist fenofibrate.
abstract: OBJECTIVE
  The peroxisome proliferator-activated receptor α (PPARα) agonist has been approved for treating hypercholesterolemia and lipid abnormalities. Researchers have recently discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. This study aims to investigate the therapeutic effects of fenofibrate on experimental autoimmune uveoretinitis (EAU).
  
  
  METHODS
  EAU was induced in Lewis rats using bovine S-antigen (S-Ag) peptide. Fenofibrate was suspended in 3% arabic gum and administered orally at a high dose of 100 mg/kg and at a low dose of 20 mg/kg every day. Fenofibrate treatment was initiated after the clinical onset once daily for 14 days. The rats were examined every other day for clinical signs of EAU. The histological scores and delayed-type hypersensitivity (DTH) were evaluated on day 28 post-immunization. Morphologic and immunohistochemical examinations were performed with light and confocal microscopy, respectively. Lymphocyte proliferation was measured with [3H] thymidine incorporation into antigen-stimulated T cells from inguinal lymph nodes.
  
  
  RESULTS
  Clinical and histological scores of EAU were decreased in the fenofibrate-treated groups. The expression of inflammatory cytokines and Müller cell proliferation were inhibited in the fenofibrate-treated groups. DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls). Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls.
  
  
  CONCLUSIONS
  The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU. Fenofibrate may be useful for treating intraocular inflammation.
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Osada
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Kuroyanagi
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kohno
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
mesh_terms: D000818:Animals; D019393:Arrestin; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D058492:Drug Repositioning; D063928:Ependymoglial Cells / Q000187:drug effects / Q000473:pathology; D011345:Fenofibrate / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D019393:Arrestin; D016207:Cytokines; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011345:Fenofibrate