TUMOR NECROSIS FACTOR-INDUCED UVEITIS IN THE LEWIS RAT IS ASSOCIATED WITH INTRAOCULAR INTERLEUKIN-6 PRODUCTION

Lewis rats were injected with recombinant murine tumour necrosis facto r-alpha either intravitreally (0.08-50 ng) or intracardially (1 mu g). The intraocular inflammatory response induced by tumour necrosis fact or was examined by slit-lamp and protein extravasation into aqueous hu mor was determined. The phenotype of the inflammatory cells in the eye was analysed by immunohistochemistry. In addition, the kinetics of in traocular interleukin 6 production were determined. At 24 hr after int ravitreal injection, a significant clinical uveitis was observed only in rats injected with 50 ng of tumour necrosis factor, when compared t o saline-treated controls (P < 0.05). Maximal clinical uveitis and blo od-aqueous barrier breakdown were already present at 4 hr after tumour necrosis factor injection. The uveitis was characterized by a massive cellular infiltrate in the anterior segment, consisting predominantly of polymorphonuclear cells and macrophages/monocytes, and to a lesser extent of T lymphocytes. Intraocular interleukin 6 mRNA expression an d elevated levels of interleukin 6 in aqueous humor were detected 1 hr after tumor necrosis factor injection, reached a maximum at 3 to 4 hr after injection, and had declined again at 2 hr. Although intracardia l injection of 1 pg of tumour necrosis factor in Lewis rats induced a rise of circulating interleukin 6, it did not produce uveitis. The res ults obtained with intravitreally injected tumour necrosis factor indi cate that intraocular TNF may play a pivotal role in the induction of uveitis in the rat. The transient intraocular production of interleuki n 6 early during tumour necrosis factor-induced uveitis suggests that this cytokine may participate in the response induced by tumour necros is factor.