Immunology Letters 141 (2011) 83–93 Contents lists available at ScienceDirect Immunology Letters jou rn al hom epage: www.elsevier.com/locate/immlet Protective effect of pristane on experimental autoimmune uveitis Jean-Baptiste Daudin a,b,1 , Dominique Monnet b,1 , Niloufar Kavian a , Cécile Espy a , Andrew Wang c , Christiane Chéreau a , Claire Goulvestre a , Samy Omri d , Antoine Brézin b , Bernard Weill a , Frédéric Batteux a,∗,1 , Carole Nicco a,1 a Université Paris Descartes, Faculté de Médecine, Hôpital Cochin, AP-HP, Laboratoire d’immunologie, EA 1833, 75679 Paris Cedex 14, France b Service d’ophtalmologie, Hôpital Cochin, AP-HP, 75679 Paris Cedex 14, France c Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA d Centre de Recherche des Cordeliers, INSERM U872, Equipe de Physiopathologie des maladies oculaires: innovations thérapeutiques, 75006 Paris, France a r t i c l e i n f o Article history: Received 23 January 2011 Received in revised form 28 July 2011 Accepted 29 July 2011 Available online 27 August 2011 Keywords: Experimental autoimmune uveitis ROS Pristane Phytol a b s t r a c t 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 IFN 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. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Experimental autoimmune uveoretinitis [1] has been studied as an animal model of birdshot retinochoroidopathy, sympathetic ophthalmia, Vogt-Koyanagi-Harada’s disease or Behc ¸ et’s disease. EAU is an organ-specific, T cell-mediated autoimmune disease that can be induced by immunization with retinal Ag [2,3], e.g., human interphotoreceptor retinoid-binding protein (IRBP) or by the adop- tive transfer of retinal Ag-specific T lymphocytes [4]. EAU is the consequence of a Th1/Th17 dominant response [5]. Augmenta- tion of the Th2 response and T regulatory cytokine production or Abbreviations: EAU, experimental autoimmune uveoretinitis; IRBP, inter- photoreceptor retinoid-binding protein; IL, interleukine; IFN, interferon; ip, intraperitoneal; NAC, N-acetylcysteine; sc, subcutaneous. ∗ Corresponding author. Tel.: +33 1 58 41 20 07; fax: +33 1 58 41 20 08. E-mail address: frederic.batteux@cch.aphp.fr (F. Batteux). 1 These authors contributed equally to this work. down-regulation of the Th1/Th17 response prevents inflammatory responses and prevents the development of EAU [6]. In human, uveitis is often associated with systemic inflamma- tory diseases such as Behc ¸ et disease, spondylarthritis or sarcoidosis. A chronic oxidative stress caused by an imbalance between pro- and anti-oxidant molecules seems to be a common feature of the chronic inflammatory state observed in those diseases. However, a correlation between the intensity of the oxidative stress and the occurrence of uveitis has been described only in Behc ¸ et’s disease [7]. Superoxide radicals are involved in the pathogenesis of experi- mental endotoxin-induced uveitis since their detoxification by the antioxidant molecule ebselen prevents the disease in both rabbits and rats [8,9]. Similarly, in vivo inhibition of iNOS by l-NAME pre- vents EAU in Lewis rats by abrogating photoreceptor apoptosis, but l-NAME spares infiltrating CD3 and CD4T cells by compro- mising their functional inactivation [10]. Paradoxically, the oral administration of the NO-donor GSNO significantly decreases auto- reactive T cell activation and diminishes the levels of inflammatory 0165-2478/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.imlet.2011.07.009