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Reply to IL-18 is not therapeutic for neovascular age-related macular degeneration

Nature Medicine volume 20, pages 1376–1377 (2014)Cite this article

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Doyle et al. reply:

Hirano et al.1 state that our data “are both perplexing and difficult to reconcile with a biological model of IL-18 signaling,” and the authors appear to be perplexed mainly by our result that systemic injection of IL-18 2 weeks before laser-induced injury afforded protection, whereas IL-18 injection 1 d before laser-induced injury did not. However, the sustained effects of IL-18 on CNV can be explained by secondary mechanisms of IL-18 action. IL-18 is a potent agonist that bridges innate and adaptive immunity, inducing the maturation and maintenance of adaptive lymphocytes, which can persist for prolonged periods of time. Some of these adaptive lymphocytes have themselves been shown to have antiangiogenic properties4, which probably explains the protracted effects of IL-18 observed when administered systemically in mice, as we discussed in our recent publication2.

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Figure 1: Mature recombinant IL-18 is not toxic in the nonhuman primate eye.

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Author information

Authors and Affiliations

  1. Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland

    Sarah L Doyle

  2. Ophthiris Discovery Performance Unit, GSK, Stevenage, UK

    Peter Adamson

  3. Ophthalmology IPE US, RD Alternative Discovery and Development, GSK, King of Prussia, Pennsylvania, USA

    Francisco J López

  4. Ocular Genetics Unit, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland

    Peter Humphries & Matthew Campbell

Authors
  1. Sarah L Doyle
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  2. Peter Adamson
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  3. Francisco J López
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  4. Peter Humphries
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  5. Matthew Campbell
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Corresponding authors

Correspondence to Sarah L Doyle or Matthew Campbell.

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Competing interests

P.A. and F.J.L. are employees of GlaxoSmithKline. Trinity College Dublin owns a patent portfolio related to the use of interleukin-18 for the treatment of age-related macular degeneration.

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Doyle, S., Adamson, P., López, F. et al. Reply to IL-18 is not therapeutic for neovascular age-related macular degeneration. Nat Med 20, 1376–1377 (2014). https://doi.org/10.1038/nm.3741

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