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


METHODS
EIU was induced by a single footpad injection of 200 microg 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.


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.


CONCLUSIONS
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.
Mangano
K
K
Department of Biomedical Sciences, University of Catania, Via Androne, Catania, Italy.
Sardesai
N Y
NY
Quattrocchi
C
C
Mazzon
E
E
Cuzzocrea
S
S
Bendtzen
K
K
Meroni
P L
PL
Kim
J J
JJ
Nicoletti
F
F
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002924:Ciliary Body / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007498:Iris / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D051996:Transcription Factor RelA / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
C518641:3-phenyl-4,5-dihydro-5-isoxazole acetic acid; D000085:Acetates; D005136:Eye Proteins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D010080:Oxazoles; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha
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