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.