title: Protective effect of pristane on experimental autoimmune uveitis.
abstract: This study evaluates the effects of pristane and phytol, two mineral oils with pro-oxidative effects, on the course of experimental autoimmune uveitis. C57BL6 mice were immunized with IRBP1-20 peptide emulsified in CFA and treated five days prior to immunization with phytol or with pristane or with PBS as control. Administration of pristane reduces the incidence and severity of IRBP-induced uveitis as demonstrated by the decrease in vasculitis and inflammatory foci in fundus and by a reduction in histological damages and leukocyte infiltration compared to untreated or phytol-treated mice. The protective effect observed is associated with a decreased activation of peripheral CD4+ and CD8+ T lymphocytes and a decrease in the intensity of the Th1 and Th17 autoimmune response to IRBP in pristane-treated mice compared to control mice, as evidenced by the decreased production of IFNγ and IL17 by IRBP-specific lymphocytes from lymph nodes draining the site of immunization and by the increased production of anti-IRBP IgG1 over IgG2a. In addition, HUVEC and ARPE-19 cells incubated with the sera of mice treated with pristane presented a reduced production of H(2)O(2). The benefit of lowering the systemic oxidative stress by pristane in the course of EAU was confirmed by injecting the antioxidant NAC in IRBP-immunized mice. As pristane, NAC decreased clinical and histological inflammation of the retina and preserved the integrity of the hemato-retinal barrier. Finally, the protective effect of pristane on the development of EAU suggests that some mineral oils may represent a new therapeutic strategy in human uveitis.
authors: Université Paris Descartes, Faculté de Médecine, Hôpital Cochin, AP-HP, Laboratoire d'immunologie, EA 1833, Paris, France.
authors: Jean-Baptiste
authors: JB
authors: Daudin
authors: Dominique
authors: D
authors: Monnet
authors: Niloufar
authors: N
authors: Kavian
authors: Cécile
authors: C
authors: Espy
authors: Andrew
authors: A
authors: Wang
authors: Christiane
authors: C
authors: Chéreau
authors: Claire
authors: C
authors: Goulvestre
authors: Samy
authors: S
authors: Omri
authors: Antoine
authors: A
authors: Brézin
authors: Bernard
authors: B
authors: Weill
authors: Frédéric
authors: F
authors: Batteux
authors: Carole
authors: C
authors: Nicco
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D005123:Eye / Q000473:pathology*; D005136:Eye Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D020381:Interleukin-17 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010836:Phytol / Q000008:administration & dosage; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000276:immunology; D013729:Terpenes / Q000008:administration & dosage*; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000111:Acetylcysteine; D005136:Eye Proteins; D006861:Hydrogen Peroxide; D007074:Immunoglobulin G; D020381:Interleukin-17; D010446:Peptide Fragments; D010836:Phytol; D012177:Retinol-Binding Proteins; D013729:Terpenes; D000099214:Retinol-Binding Proteins, Interstitial; C009042:pristane