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

Fingerprint

Uveitis
Immunologic Factors
Endotoxins
Lipopolysaccharides
Animal Disease Models
Inbred NOD Mouse
Experimental Arthritis
Eye Diseases
Aqueous Humor
Colitis
Type 1 Diabetes Mellitus
Dexamethasone
Molecular Weight
3-phenyl-4,5-dihydro-5-isoxazole acetic acid
Injections
Therapeutics
Pharmaceutical Preparations

Keywords

  • Cytokines
  • Immunotherapy
  • Uveitis
  • VGX-1027

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mangano, K., Sardesai, N. Y., Quattrocchi, C., Mazzon, E., Cuzzocrea, S., Bendtzen, K., ... 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

Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats. / Mangano, K.; Sardesai, N. Y.; Quattrocchi, C.; Mazzon, E.; Cuzzocrea, S.; Bendtzen, K.; Meroni, P. L.; Kim, J. J.; Nicoletti, F.

In: British Journal of Pharmacology, Vol. 155, No. 5, 11.2008, p. 722-730.

Research output: Contribution to journalArticle

Mangano, K, Sardesai, NY, Quattrocchi, C, Mazzon, E, Cuzzocrea, S, Bendtzen, K, Meroni, PL, Kim, JJ & Nicoletti, F 2008, 'Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats', British Journal of Pharmacology, vol. 155, no. 5, pp. 722-730. https://doi.org/10.1038/bjp.2008.315
Mangano, K. ; Sardesai, N. Y. ; Quattrocchi, C. ; Mazzon, E. ; Cuzzocrea, S. ; Bendtzen, K. ; Meroni, P. L. ; Kim, J. J. ; Nicoletti, F. / Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats. In: British Journal of Pharmacology. 2008 ; Vol. 155, No. 5. pp. 722-730.
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