The effect of thalidomide and supidimide on endotoxin-induced uveitis in rats.
BACKGROUND
Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation, produced by footpad injection of endotoxin (lipopolysaccharide, LPS) to mimic the human disease of acute anterior uveitis, that is useful for testing new anti-inflammatory therapy. The purpose of this study was to test the anti-inflammatory effect on EIU of thalidomide and one of its derivatives, supidimide.


METHODS
EIU was produced in rats by hind foot-pad injection of LPS (100 micrograms/animal). Animals were killed 20 h after LPS injection. Inflammation was evaluated by anterior chamber determination of proteins and cells.


RESULTS
A dosage of 400 mg/kg per day of thalidomide was efficient in reducing inflammation whether given in three doses (at -24 h, -4 h and +4 h relative to LPS challenge = THAL-1; p < 0.001 for proteins and cells), in two doses (-4 h and +4 h = THAL-2; p < 0.001 for proteins, p < or = 0.012 for cells) or in one dose (at +4 h = late THAL; p < 0.001 for proteins, p < or = 0.02 for cells). A dosage of 300 mg/kg per day of thalidomide was still efficient (p < or = 0.023 for proteins, p < or = 0.06 for cells), but 150 mg/kg per day had no effect on inflammation. Supidimide (400 mg/kg per day) had some anti-inflammatory effect (p < or = 0.053 for proteins, p < or = 0.06 for cells).


CONCLUSIONS
High-dose thalidomide had a potent anti-inflammatory effect in EIU, but lower doses were not sufficient to reduce inflammation. At similar high doses, supidimide had some effect on EIU but was less effective than thalidomide.
Guex-Crosier
Y
Y
Hôpital Jules Gonin, Department of Ophthalmology, University of Lausanne, Switzerland.
Pittet
N
N
Herbort
C P
CP
D000208:Acute Disease; D000818:Animals; D000867:Anterior Chamber / Q000473:pathology; D001082:Aqueous Humor; D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*
D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; C027952:salmonella toxin; D013792:Thalidomide; C027948:supidimide