Interleukin-18 regulates pathological intraocular neovascularization

Hong Qiao, Kohei Sonoda, Yasuhiro Ikeda, Takeru Yoshimura, Kuniaki Hijioka, Young Joon Jo, Yukio Sassa, Chikako Tsutsumi-Miyahara, Yasuaki Hata, Shizuo Akira, Tatsuro Ishibashi

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29 Citations (Scopus)

Abstract

Recently, the proinflammatory cytokine IL-18 has been shown to have a role in angiogenesis. This study aimed to elucidate its role in abnormal neovascularization (NV) in an oxygen-induced retinopathy (OIR) mouse model of the retinopathy seen in human premature newborns. IL-18 was constitutively expressed in the retina in C57BL/6 mice, but expression transiently dropped on Day 17 after birth in mice exposed to 75% oxygen for 5 days between Days 7 and 12. Coincident with the IL-18 reduction in oxygen-treated mice, vascular endothelial growth factor was expressed in the retina, and OIR developed. By Day 24, NV in the retina had regressed to normal levels. By contrast, IL-18 knockout mice, exposed to elevated oxygen concentrations, developed more severe OIR on Day 17, and it is important that this persisted until Day 24. This suggested that IL-18 negatively regulated retinal NV. To investigate this further, we administrated recombinant IL-18 to C57BL/6 mice during the development of OIR but found no significant inhibition of retinopathy. However, when IL-18-binding protein was administered during the OIR recovery phase to neutralize endogenous IL-18, OIR was still apparent on Day 24. We therefore concluded that IL-18 regulates pathogenic retinal NV by promoting its regression rather than inhibiting its development. This suggests some useful, new approaches to treating retinopathy in humans.

Original languageEnglish
Pages (from-to)1012-1021
Number of pages10
JournalJournal of Leukocyte Biology
Volume81
Issue number4
DOIs
Publication statusPublished - Apr 1 2007

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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