Endotoxin-induced uveitis (EIU) in mice with IL-1 receptor and TNF receptor genes deleted

Stephen Planck, Y. B. Han, J. M. Park, B. Brito, L. O'Rourke, X. N. Huang, James (Jim) Rosenbaum

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Abstract

Purpose: To determine the role of interleukin-1 (IL-1) and tumor necrosis factor a (TNF) in the pathogenesis of EIU. Methods: 250 ng E.coli endotoxin was injected into the vitreous of mice deficient in IL-1 receptor type I (IL-1R1-/-), TNF receptors p55 and p75 (TNFRSS/75-/-), IL-IR1-/-/TNFR55-/-) or congenic controls (Immunex, Seattle, WA).. Eyes were harvested after 24 h for histologie analysis and collection of aqueous humor or after 3 h for RT-PCR analysis. IL-6 activity in aqueous humor was measured with a B9 cell bioassay. Results: No significant difference in the number of infiltrating cells was found in TNFR55/75-/- mice compared to controls in any of 4 separate experiments or in the combined data (total n= 38). The number of infiltrating cells was significantly reduced in 2 experiments with IL-lRl-/- mice (p-/- /TNFRSS''' mice had a reduction in infiltrating cells in 2 of 3 experiments and in the combined data (all p-/- mice, but were reduced in 1 of 2 experiments with IL-1R1-/- mice (n=8, p=0.02) and in 1 experiment with IL-1R1-/-/TNFR55-/- mice (n=12, p=0.01). Conclusions IL-1 appears to have a more pivotal role in EIU than TNF, although neither cytokine is essential. Deletion of receptors for both cytokines has the most pronounced effect which is in accord with the hypothesis that these cytokines are, at least in part, functionally redundant. NIH grants: EYO6468, EYO6477, EY10572.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
Publication statusPublished - 1997

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ASJC Scopus subject areas

  • Ophthalmology

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