Exogenous nitric oxide inhibits experimental autoimmune uveoretinitis development in Lewis rats by modulation of the Th1-dependent immune response.

Abstract

Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease of posterior uvea that closely resembles a human disease. The uveitogenic effector T cell has a Th1-like phenotype [high interferon-gamma (IFN-gamma), low interleukin-4 (IL-4)], and genetic susceptibility to EAU that is associated with an elevated Th1 response. Suppression of CD4+ Th1 cells for the treatment of autoimmune disease is an attractive potential therapeutic approach. Nitric oxide (NO) has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. In this study, we investigated the potential role of NO as an immunoregulator to alter Th1/Th2 cytokine production, as well as to inhibit the interphotoreceptor retinoid binding protein (IRBP)-induced EAU, a CD4+ Th1 cell-mediated autoimmune disease. Injection of IRBP (100 microg) into two footpads resulted in severe EAU. The beginning peak of the disease was days 12 to 15 after immunization. Oral treatment with molsidomine (MSDM), a NO donor, began 24 h before IRBP immunization to the end of the experiments, which resulted in a significant inhibition of the disease by clinical and histopathological criteria. When MSDM was administered until day 21, a complete reduction of incidence and severity of EAU was observed. To investigate the cytokine alterations from Th1 to Th2 cytokines by MSDM, the cytokines were assayed in a culture medium of IRBP-stimulated inguinal lymphocytes. IRBP-immunized rats secreted a high concentration of IFN-gamma and a low concentration of IL-10. In contrast, MSDM treatment enhanced IL-10 secretion and tended to decrease IFN-gamma secretion. In conclusion, we show that the administration of NO suppresses EAU by altering the Th1/Th2 balance of inflammatory immune responses. We suggest that NO may be useful in the therapeutic control of autoimmune uveitis.

• Authors: H J Kwak, Y S Yang, H O Pae, Y M Kim, H T Chung
• Journal: Molecules and cells (Mol Cells) Vol. 12 Issue 2 Pg. 178-84 (Oct 31 2001) ISSN: 1016-8478 [Print] Korea (South)
• PMID: 11710518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Eye Proteins
• Nitric Oxide Donors
• Retinol-Binding Proteins
• interstitial retinol-binding protein
• Interleukin-10
• Nitric Oxide
• Interferon-gamma
• Molsidomine

Topics

• Animals
• Autoimmune Diseases (immunology, pathology, prevention & control)
• Disease Models, Animal
• Eye Proteins
• Humans
• Immunization
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• Male
• Molsidomine (pharmacology)
• Nitric Oxide (immunology)
• Nitric Oxide Donors (pharmacology)
• Rats
• Rats, Inbred Lew
• Retinitis (immunology, pathology, prevention & control)
• Retinol-Binding Proteins (immunology)
• Th1 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)
• Uveitis (immunology, pathology, prevention & control)