Ocular inflammatory effects of intravitreally injected interleukin-2.
The primary, known physiologic effect of interleukin-2 (IL-2) is to act as a T lymphocyte growth factor. We investigated the potential contribution of IL-2 to intraocular inflammation by studying the inflammation resulting from the intravitreal injection of recombinant, human IL-2 in New Zealand white rabbits. Serial slit lamp observations indicated that 40 microgram of intravitreally injected IL-2 induced an anterior uveitis which was maximal 5 days after the injection. Inflammation was less marked but still significant with amounts of IL-2 as low as 400 ng. Direct examination of aqueous humor confirmed elevations of protein, prostaglandin E2, and mononuclear cells which correlated with the clinical observations. The kinetics of the response to intravitreal IL-2 distinguished it from the responses to other intravitreally injected cytokines such as interleukins 1, 6, or 8 as well as tumor necrosis factor. Intramuscular injection of cyclosporine A significantly reduced the protein extravasation associated with IL-2 injection, but cyclosporine had no effect on inflammation secondary to an intravitreal injection of interleukin-1. These observations implicate IL-2 as a potential contributor to uveitis. In addition, the studies with cyclosporine indicate the heterogeneity of inflammation such that pharmacologic agents which affect one cause of uveitis are not necessarily efficacious in another model.
Samples
J R
JR
Department of Ophthalmology, Oregon Health Sciences University, Casey Eye Institute, Portland 97201.
Boney
R S
RS
Rosenbaum
J T
JT
D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000187:drug effects; D002452:Cell Count; D016572:Cyclosporine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D007267:Injections; D007273:Injections, Intramuscular; D007376:Interleukin-2 / Q000633:toxicity*; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity; D014606:Uveitis, Anterior / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D014822:Vitreous Body
D005136:Eye Proteins; D007376:Interleukin-2; D011994:Recombinant Proteins; D016572:Cyclosporine; D015232:Dinoprostone