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Activity of an interleukin 1 receptor antagonist in rabbit models of uveitis.

Abstract
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.
AuthorsJ T Rosenbaum, R S Boney
JournalArchives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 110 Issue 4 Pg. 547-9 (Apr 1992) ISSN: 0003-9950 [Print] United States
PMID1532889 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Endotoxins
  • Eye Proteins
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Proteins
  • Recombinant Proteins
  • Sialoglycoproteins
  • endotoxin, Escherichia coli
Topics
  • Animals
  • Aqueous Humor (chemistry, cytology)
  • Arthus Reaction
  • Cell Count
  • Disease Models, Animal
  • Endotoxins
  • Escherichia coli
  • Eye Proteins (analysis)
  • Female
  • Injections
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Male
  • Proteins (administration & dosage, pharmacology)
  • Rabbits
  • Recombinant Proteins (administration & dosage, pharmacology)
  • Sialoglycoproteins
  • Uveitis, Anterior (etiology, pathology, prevention & control)

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