Interleukin-18 inhibits experimental choroidal neovascularization and its potential therapeutic applications_Chinese Journal of Ocular Fundus Diseases

Authors：

XiaoYanling ,  WuYuyu

Department of Ophtalmology, Second Affiliated Hospital of Fujian Medical University, Fuzhou 362000, China;

Corresponding author：

WuYuyu, Email: 13506095998@126.com

Keywords：

Choroidal neovascularization/therapy; Interleukin-18/antagonists & inhibitors; Review

DOI：

10.3760/cma.j.issn.1005-1015.2016.04.030

Video：

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Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.

Citation： XiaoYanling, WuYuyu. Interleukin-18 inhibits experimental choroidal neovascularization and its potential therapeutic applications. Chinese Journal of Ocular Fundus Diseases, 2016, 32(4): 457-459. doi: 10.3760/cma.j.issn.1005-1015.2016.04.030 Copy

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13.	Battle TE, Lynch RA, Frank DA. Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis[J]. Cancer Res, 2006, 66(7):3649-3657.
14.	Nakajima H, Brindle PK, Handa M, et al. Functional interaction of STAT5 and nuclear receptor co-repressor SMRT:implications in negative regulation of STAT5-dependent transcription[J]. EMBO J, 2001, 20(23):6836-6844.
15.	Friesel R, Komoriya A, Maciag T. Inhibition of endothelial cell proliferation by g-interferon[J]. J Cell Biol, 1987, 104(3):689-696.
16.	Sancéau J, Boyd DD, Seiki M, et al. Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B[J]. J Biol Chem, 2002, 277(38):35766-36775.
17.	Sheibani N, Newman PJ, Frazier WA. Thrombospondin-1, a natural inhibitor of angiogenesis, regulates platelet-endothelial cell adhesion molecule-1 expression and endothelial cell morphogenesis[J]. Mol Biol Cell, 1997, 8(7):1329-1341.
18.	Sheibani N, Frazier WA. Thrombospondin-1, PECAM-1, and regulation of angiogenesis[J]. Histol Histopathol, 1999, 14(1):285-294.
19.	Jiménez B, Volpert OV, Crawford SE, et al.Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1[J]. Nat Med, 2000, 6(1):41-48.
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21.	Doyle SL, López FJ, Celkova L, et al. IL-18 immunotherapy for neovascular AMD:tolerability and efficacy in nonhuman primates[J]. Invest Ophthalmol Vis Sci, 2015, 56(9):5424-5430. DOI:10.1167/iovs.15-17264.
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1. CATT Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration[J]. N Engl J Med, 2011,364(20):1897-1908. DOI 10.1056/NEJMoa1102673.
2. Doyle SL, Ozaki E, Brennan K, et al. IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration[J/OL]. Sci Transl Med, 2014, 6(230):230ra44[2014-04-02]. http://stm.sciencemag.org/content/6/230/230ra44.short. DOI:10.1126/scitranslmed.3007616.
3. Novick D, Kim S, Kaplanski G, et al. Interleukin-18, more than a th1cytokine[J]. Semin Immunol, 2013, 25(6):439-448. DOI:10.1016/j.smim.2013.10.014.
4. Smith DE. The biological paths of IL-1 family members IL-18 and IL-33[J]. Leukoc Biol, 2011,89(3):383-392. DOI:10.1189/jlb.0810470.
5. Okamura H, Nagata K, Komatsu T, et al. A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock[J]. Infect Immun, 1995, 63:3966-3972.
6. Cao R, Farnebo J, Kurimoto M, et al. Interleukin-18 acts as an angiogenesis and tumor suppressor[J]. FASEB J,1999,13(15):2195-202.
7. Qiao H, Sonoda KH, Sassa Y, et al. Abnormal retinal vascular development in IL-18 knockout mice[J]. Lab Invest, 2004, 84(8):973-980.
8. Qiao H, Sonoda KH, Ikeda Y, et al. Interleukin-18 regulates pathological intraocular neovascularization[J]. J Leukoc Biol, 2007, 81(4):1012-1021.
9. Doyle SL, Campbell M, Ozaki E, et al. NLRP3 plays a protective role during the development of age related macular degeneration through the induction of IL-18 by drusen components[J]. Nat Med, 2012, 18(5):791-798. DOI:10.1038/nm.2717.
10. Shen J, Choy DF, Yoshida T, et al. Interleukin-18 has antipermeablity and antiangiogenic activities in the eye:reciprocal suppression with VEGF[J].Cell Physiol, 2014, 229(8):974-983. DOI:10.1002/jcp.24575.
11. Duluc D, Corvaisier M, Blanchard S, et al Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages[J]. Int J Cancer, 2009, 125(2):367-373. DOI:10.1002/ijc.24401.
12. Sun T, Yang Y, Luo X, et al.Inhibition of tumor angiogenesis by interferon-γ by suppression of tumor-associated macrophage differentiation[J].Oncol Res, 2014, 21(5):227-235. DOI:10.3727/096504014X13890370410285.
13. Battle TE, Lynch RA, Frank DA. Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis[J]. Cancer Res, 2006, 66(7):3649-3657.
14. Nakajima H, Brindle PK, Handa M, et al. Functional interaction of STAT5 and nuclear receptor co-repressor SMRT:implications in negative regulation of STAT5-dependent transcription[J]. EMBO J, 2001, 20(23):6836-6844.
15. Friesel R, Komoriya A, Maciag T. Inhibition of endothelial cell proliferation by g-interferon[J]. J Cell Biol, 1987, 104(3):689-696.
16. Sancéau J, Boyd DD, Seiki M, et al. Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B[J]. J Biol Chem, 2002, 277(38):35766-36775.
17. Sheibani N, Newman PJ, Frazier WA. Thrombospondin-1, a natural inhibitor of angiogenesis, regulates platelet-endothelial cell adhesion molecule-1 expression and endothelial cell morphogenesis[J]. Mol Biol Cell, 1997, 8(7):1329-1341.
18. Sheibani N, Frazier WA. Thrombospondin-1, PECAM-1, and regulation of angiogenesis[J]. Histol Histopathol, 1999, 14(1):285-294.
19. Jiménez B, Volpert OV, Crawford SE, et al.Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1[J]. Nat Med, 2000, 6(1):41-48.
20. Kim J, Kim C, Kim TS,et al. IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway[J]. Biochem Biophys Res Commun, 2006, 344(4):1284-1289.
21. Doyle SL, López FJ, Celkova L, et al. IL-18 immunotherapy for neovascular AMD:tolerability and efficacy in nonhuman primates[J]. Invest Ophthalmol Vis Sci, 2015, 56(9):5424-5430. DOI:10.1167/iovs.15-17264.
22. Ijima R, Kaneko H, Ye F, et al. Interleukin-18 induces retinal pigment epithelium degeneration in mice[J]. Invest Ophthalmol Vis Sci, 2014, 55(10):6673-6678. DOI:10.1167/iovs.14-15367.

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