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

S. R. Planck, Y. B. Han, J. M. Park, B. Brito, L. O'Rourke, X. N. Huang, J. T. Rosenbaum

Research output: Contribution to journalArticlepeer-review

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<0.001, <0.01), but not in 2 others. The combined data did show a reduction (p<0.001). IL-1R1-/- /TNFRSS''' mice had a reduction in infiltrating cells in 2 of 3 experiments and in the combined data (all p<0.001). IL-6 activity in aqueous humor was not correlated with the number of infiltrating cells in the contralateral eye. IL-6 levels were not significantly reduced in either of two experiments with TNFR55/75-/- 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)
Pages (from-to)S188
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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