Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies

Curr Eye Res. 2000 Feb;20(2):109-14.

Abstract

Purpose: The role of macrophage migration inhibitory factor (MIF) in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) in rats following immunization with a retinal antigen (Ag), interphotoreceptor retinoid-binding protein (IRBP).

Methods: LEW rats were immunized with a single injection of IRBP derived peptide, R16(ADGSSWEGVGVVPDV). A neutralizing monoclonal antibody (mAb, IgM) to MIF was injected intraperitoneally every second day from day 0 to day 6 (group A), or from day 8 to day 14 (group B). Control rats were treated with unrelated mouse IgM or PBS. T cell proliferative responses were measured 12 days after immunization. The occurrence and severity of EAU were observed and compared among experimental and control groups.

Results: T cell proliferative responses against R16 were inhibited in rats treated with anti-MIF mAb compared with the control rats. The development of EAU was delayed in the rats of group A in comparison with those of group B and the control group. The mean histological EAU score on day 18 in group A was 1.11 +/- 0. 11 and significantly lower than those of the group B (1.29 +/- 0.19) and the control (1.67 +/- 0.19).

Conclusions: The present result suggests that MIF plays an important role in induction of EAU.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Autoimmune Diseases / chemically induced
  • Autoimmune Diseases / prevention & control*
  • Eye / drug effects
  • Eye / pathology
  • Eye Proteins*
  • Injections, Intraperitoneal
  • Macrophage Migration-Inhibitory Factors / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Rats
  • Rats, Inbred Lew
  • Retinitis / chemically induced
  • Retinitis / prevention & control*
  • Retinol-Binding Proteins / chemistry
  • Severity of Illness Index
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Uveitis / chemically induced
  • Uveitis / prevention & control*

Substances

  • Antibodies, Monoclonal
  • Eye Proteins
  • Macrophage Migration-Inhibitory Factors
  • Peptide Fragments
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein