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.