Tumour Necrosis Factor-Induced Uveitis in the Lewis Rat Is Associated With Intraocular Interleukin 6 Production

Exp Eye Res. 1995 Feb;60(2):199-207. doi: 10.1016/s0014-4835(95)80011-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aqueous Humor / metabolism
  • Blotting, Northern
  • Dose-Response Relationship, Drug
  • Eye / pathology
  • Gene Expression
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Kinetics
  • Male
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / toxicity
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / toxicity*
  • Uveitis, Anterior / etiology*
  • Uveitis, Anterior / metabolism
  • Uveitis, Anterior / pathology

Substances

  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha