Studies on intraocular inflammation produced by intravitreal human interleukins in rabbits.
Recombinant human interleukin-1 alpha, interleukin-1 beta (10, 80 or 200 units), interleukin-8 (10 or 40 units) or endotoxin was injected intravitreally into rabbit eyes. Twenty-four hours thereafter aqueous humor protein, leukocyte number, prostaglandin E2, leukotriene B4 and rabbit interleukin-1 beta were measured. In addition, synthesis of prostaglandin E2 and leukotriene B4 in iris-ciliary body and myeloperoxidase (MPO) activity were determined. Recombinant human interleukins 1 alpha and 1 beta, but not interleukin-8 induced signs of uveitis, i.e. protein and leukocytic infiltration into aqueous humor. At 200 unit activities, human interleukin-1 beta was significantly greater than interleukin-1 alpha in causing leukocyte infiltration response. Interleukin-1 alpha did not stimulate the release of prostaglandin E2 or leukotriene B4. In fact, interleukin-1 beta significantly inhibited the synthesis of prostaglandin E2 in iris-ciliary body. Both of these human interleukins caused a release of rabbit interleukin-1 beta in aqueous achieving a level significantly higher than observed after endotoxin injection. This study demonstrates that intravitreal injections of human IL-1 alpha and IL-1 beta induce uveitis by releasing rabbit interleukin-1 beta within the eye.
Kulkarni
P S
PS
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Research Institute, University of Louisville, School of Medicine 40292.
Mancino
M
M
D000818:Animals; D001082:Aqueous Humor / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D002924:Ciliary Body / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis; D004731:Endotoxins / Q000633:toxicity; D007375:Interleukin-1 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism* / Q000633:toxicity*; D007498:Iris / Q000502:physiology; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D009195:Peroxidase / Q000096:biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D014605:Uveitis / Q000139:chemically induced*
D004731:Endotoxins; D007375:Interleukin-1; D007378:Interleukins; D011994:Recombinant Proteins; D007975:Leukotriene B4; D009195:Peroxidase; D015232:Dinoprostone