Activity of an interleukin 1 receptor antagonist in rabbit models of uveitis.
Interleukin 1 has been implicated in intraocular inflammation. The availability of a cloned, recombinant interleukin 1 receptor antagonist has enabled us to test the role of interleukin 1 in specific models of uveitis in New Zealand white rabbits. Seventy-five micrograms of interleukin 1 receptor antagonist injected intravitreally resulted in a 97% reduction in aqueous humor cells present 6 hours after intravitreal injection of 10 ng of human interleukin 1 alpha. Disruption of the blood aqueous barrier was prevented by the receptor antagonist (mean +/- SD aqueous humor protein of 0.6 +/- 0.1 g/L in rabbits treated with interleukin 1 receptor antagonist vs 32.2 +/- 9.9 g/L in controls). Lower doses of interleukin 1 produced more modest but significant inhibition. Despite the activity of interleukin 1 receptor antagonist in inhibiting interleukin 1-induced inflammation, interleukin 1 receptor antagonist did not produce significant reduction in inflammation subsequent to an active Arthus reaction or subsequent to the intravitreal injection of 125 ng of endotoxin. A potential explanation of these observations is that cytokines in addition to interleukin 1 may be present in sufficient quantities to produce intraocular inflammation or that the effects of interleukin 1 may be primarily intracellular (intracrine) and therefore resistant to the activity of exogenously administered receptor antagonist.
Rosenbaum
J T
JT
Oregon Health Sciences University, Portland 97201.
Boney
R S
RS
D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000166:cytology; D001183:Arthus Reaction; D002452:Cell Count; D004195:Disease Models, Animal; D004731:Endotoxins; D004926:Escherichia coli; D005136:Eye Proteins / Q000032:analysis; D005260:Female; D007267:Injections; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008297:Male; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012795:Sialoglycoproteins; D014606:Uveitis, Anterior / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D004731:Endotoxins; D005136:Eye Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011506:Proteins; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C044101:endotoxin, Escherichia coli