Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats

K. Mangano, N. Y. Sardesai, C. Quattrocchi, E. Mazzon, S. Cuzzocrea, K. Bendtzen, P. L. Meroni, J. J. Kim, F. Nicoletti

Research output: Contribution to journalArticle

Abstract

Background and purpose: VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis. Here, we have studied the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans. Experimental approach: EIU was induced by a single footpad injection of 200 μg lipopolysaccharide (LPS). Groups of rats were treated with either VGX-1027 (25 mg kg -1) or its vehicle at different time points (30 min, 6 h or 12 h) after the challenge with LPS or, as positive control, with dexamethasone. The rats were killed within 16 h after LPS challenge, and the eyes and aqueous humor were collected to study serological, immunological and histological signs of EIU. Key results: The rats treated with VGX-1027 within 6 h after LPS challenge exhibited milder clinical, histological and laboratory signs of EIU than those treated with vehicle. Conclusion and implications: This study provides the first evidence that systemic treatment with VGX-1027 counteracts the uveitis-inducing effect of LPS in rats and suggests that this drug may have potential in the treatment of immuno-inflammatory conditions of the eye in humans.

Original languageEnglish
Pages (from-to)722-730
Number of pages9
JournalBritish Journal of Pharmacology
Volume155
Issue number5
DOIs
Publication statusPublished - Nov 2008

Keywords

  • Cytokines
  • Immunotherapy
  • Uveitis
  • VGX-1027

ASJC Scopus subject areas

  • Pharmacology

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    Mangano, K., Sardesai, N. Y., Quattrocchi, C., Mazzon, E., Cuzzocrea, S., Bendtzen, K., Meroni, P. L., Kim, J. J., & Nicoletti, F. (2008). Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats. British Journal of Pharmacology, 155(5), 722-730. https://doi.org/10.1038/bjp.2008.315