Interleukin-1β Inhibition Prevents Choroidal Neovascularization and Does Not Exacerbate Photoreceptor Degeneration

Abstract

The IL-1 family of cytokines plays a key role in the initiation of acute inflammatory responses.¹ x 1 Dinarello, C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009; 27: 519–550 Crossref | PubMed | Scopus (1707) | Google Scholar See all References IL-1β interacts with IL-1 receptor I (IL-1RI), composed of IL-1R and IL-1R accessory protein subunits. IL-1 receptor antagonist (IL-1Ra) competes with IL-1β for its binding site.¹ x 1 Dinarello, C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009; 27: 519–550 Crossref | PubMed | Scopus (1707) | Google Scholar See all References IL-1β is a potent inflammatory mediator with chemotactic² x 2 Isoda, K., Sawada, S., Ishigami, N., Matsuki, T., Miyazaki, K., Kusuhara, M., Iwakura, Y., and Ohsuzu, F. Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2004; 24: 1068–1073 Crossref | PubMed | Scopus (93) | Google Scholar See all References and angiogenic³ x 3 BenEzra, D., Hemo, I., and Maftzir, G. In vivo angiogenic activity of interleukins. Arch Ophthalmol. 1990; 108: 573–576 Crossref | PubMed | Scopus (84) | Google Scholar See all References ^{, 4} x 4 Carmi, Y., Voronov, E., Dotan, S., Lahat, N., Rahat, M.A., Fogel, M., Huszar, M., White, M.R., Dinarello, C.A., and Apte, R.N. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009; 183: 4705–4714 Crossref | PubMed | Scopus (119) | Google Scholar See all References properties. It is a neurotoxic mediator in ischemic brain injury⁵ x 5 Yamasaki, Y., Matsuura, N., Shozuhara, H., Onodera, H., Itoyama, Y., and Kogure, K. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke. 1995; 26: 676–680 Crossref | PubMed | Google Scholar See all References but can attenuate glutamate neurotoxicity in the retina⁶ x 6 Namekata, K., Harada, C., Guo, X., Kikushima, K., Kimura, A., Fuse, N., Mitamura, Y., Kohyama, K., Matsumoto, Y., Tanaka, K., and Harada, T. Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice. Neurosci Lett. 2009; 465: 160–164 Crossref | PubMed | Scopus (17) | Google Scholar See all References and protect against light-induced or hereditary photoreceptor degeneration.⁷ x 7 LaVail, M.M., Unoki, K., Yasumura, D., Matthes, M.T., Yancopoulos, G.D., and Steinberg, R.H. Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci U S A. 1992; 89: 11249–11253 Crossref | PubMed | Scopus (582) | Google Scholar See all References ^{, 8} x 8 Whiteley, S.J., Klassen, H., Coffey, P.J., and Young, M.J. Photoreceptor rescue after low-dose intravitreal IL-1beta injection in the RCS rat. Exp Eye Res. 2001; 73: 557–568 Crossref | PubMed | Scopus (19) | Google Scholar See all References