Activity of an interleukin 1 receptor antagonist in rabbit models of uveitis
J. T. Rosenbaum and R. S. Boney
Oregon Health Sciences University, Portland 97201.
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.
