title: Tumour necrosis factor-induced uveitis in the Lewis rat is associated with intraocular interleukin 6 production.
abstract: Lewis rats were injected with recombinant murine tumour necrosis factor-alpha either intravitreally (0.08-50 ng) or intracardially (1 microgram). The intraocular inflammatory response induced by tumour necrosis factor was examined by slit-lamp and protein extravasation into aqueous humor was determined. The phenotype of the inflammatory cells in the eye was analysed by immunohistochemistry. In addition, the kinetics of intraocular interleukin 6 production were determined. At 24 hr after intravitreal injection, a significant clinical uveitis was observed only in rats injected with 50 ng of tumour necrosis factor, when compared to saline-treated controls (P < 0.05). Maximal clinical uveitis and blood-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 and 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 intracardial injection of 1 microgram of tumour necrosis factor in Lewis rats induced a rise of circulating interleukin 6, it did not produce uveitis. The results obtained with intravitreally injected tumour necrosis factor indicate that intraocular TNF may play a pivotal role in the induction of uveitis in the rat. The transient intraocular production of interleukin 6 early during tumour necrosis factor-induced uveitis suggests that this cytokine may participate in the response induced by tumour necrosis factor.
authors.affiliation: Department of Ophthalmo-Immunology, The Netherlands Ophthalmic Research Institute, Amsterdam.
authors.forename: A F
authors.initials: AF
authors.lastname: De Vos
authors.forename: M A
authors.initials: MA
authors.lastname: Van Haren
authors.forename: C
authors.initials: C
authors.lastname: Verhagen
authors.forename: R
authors.initials: R
authors.lastname: Hoekzema
authors.forename: A
authors.initials: A
authors.lastname: Kijlstra
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000473:pathology; D015870:Gene Expression; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000633:toxicity*; D014606:Uveitis, Anterior / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha