Suppression of experimental autoimmune uveoretinitis by Anti-IL-17 antibody

Curr Eye Res. 2009 Apr;34(4):297-303. doi: 10.1080/02713680902741696.

Abstract

Purpose: To determine whether treatment with anti-IL-17 antibody could suppress the intraocular inflammation of experimental autoimmune uveoretinitis (EAU) in rats.

Methods: Rats were immunized with interphotoreceptor retinoid binding protein (IRBP) R16 peptide and were treated with anti-IL-17 antibody. Clinical signs of inflammation and ocular histological sections were observed and graded. Cytokine levels of supernatants of cells from draining lymph nodes were measured by enzyme-linked immunosorbent assay (ELISA). Delayed-type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) were detected.

Results: Treatment of EAU with anti-IL-17 antibody delayed the onset of ocular inflammation and markedly inhibited the development of EAU. Antigen-specific DTH and LPA were suppressed, whereas the level of interferon (IFN)-gamma produced by draining lymph node cells was increased after treatment with anti-IL-17 antibody. There was no significant change of IL-5 level as compared with control rats.

Conclusions: These findings demonstrate that blockade of endogenous IL-17 activity by treatment with anti-IL-17 antibody attenuates EAU in rats. IL-17 rather than IFN-gamma plays a crucial role in the development of EAU, and that antagonism of IL-17 could be useful for the treatment of human intraocular autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / physiopathology
  • Autoimmune Diseases / prevention & control*
  • Cell Proliferation / drug effects
  • Eye Proteins / immunology
  • Female
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / physiopathology
  • Interferon-gamma / metabolism
  • Interleukin-17 / immunology*
  • Lymph Nodes / metabolism
  • Lymphocytes / pathology
  • Rats
  • Rats, Inbred Lew
  • Retinitis / pathology*
  • Retinol-Binding Proteins / immunology
  • Up-Regulation
  • Uveitis / pathology*

Substances

  • Antibodies
  • Eye Proteins
  • Interleukin-17
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein
  • Interferon-gamma