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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-08-2014 | Retinal Disorders

Increased intravitreous interleukin-18 correlated to vascular endothelial growth factor in patients with active proliferative diabetic retinopathy

Authors: Zongming Song, Min Sun, Fen Zhou, Fang Huang, Jia Qu, Ding Chen

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 8/2014

Abstract

Purpose

To determine the intravitreous levels of interleukin-18 (IL-18) and vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to ascertain their association with PDR activity.

Methods

Thirty eyes of 30 diabetic patients with PDR were divided into two groups (active PDR, n = 17; quiescent PDR, n = 13). Fifteen eyes of 15 non-diabetic patients (macular hole, n = 9; epiretinal membrane, n = 6) served as controls. All vitreous fluid samples were obtained during vitrectomy. IL-18 and VEGF were measured by enzyme-linked immunosorbent assay. Serum glycosylated hemoglobin as well as the basic demographic data was documented.

Results

Both IL-18 and VEGF levels were higher in patients with PDR than control (P < 0 .01 and P < 0 .01, respectively). Both IL-18 and VEGF in active PDR were higher than those in quiescent PDR (P = 0.048 and P = 0.03, respectively). A significant positive correlation (Spearman rank correlation coefficient (r _s) = 0.502, P = 0.005) between IL-18 and VEGF was observed in all PDR patients but not in the control. The correlation between VEGF and IL-18 was even stronger in the subgroup of active PDR (r _s = 0.684; P = 0.002), whereas no significant correlation was found in the subgroup of quiescent PDR (r _s = 0.049; P = 0.873).

Conclusions

Both intravitreous IL-18 and VEGF were elevated in patients with PDR, which were closely correlated in active PDR. IL-18 may contribute to retinal angiogenesis by acting together with or via VEGF, and become the potential therapeutic target for treatment of PDR.

Adamis AP, Miller JW, Bernal MT et al (1994) Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 118:445–450PubMed

Aiello LP, Avery RL, Arrigg PG et al (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487PubMedCrossRef

Mahdy RA, Nada WM, Hadhoud KM, El-Tarhony SA (2010) The role of vascular endothelial growth factor in the progression of diabetic vascular complications. Eye 24:1576–1584PubMedCrossRef

Matsunaga N, Chikaraishi Y, Izuta H et al (2008) Role of soluble vascular endothelial growth factor receptor-1 in the vitreous in proliferative diabetic retinopathy. Ophthalmology 115:1916–1922PubMedCrossRef

Chen E, Park CH (2006) Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina 26:699–700PubMedCrossRef

di Lauro R, De Ruggiero P, di Lauro R et al (2010) Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 248:785–791PubMedCrossRef

Chung EJ, Kang SJ, Koo JS et al (2011) Effect of intravitreal bevacizumab on vascular endothelial growth factor expression in patients with proliferative diabetic retinopathy. Yonsei Med J 52:151–157PubMedCentralPubMedCrossRef

Joussen AM, Poulaki V, Le ML et al (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. Faseb J 18:1450–1452PubMed

Spijkerman AM, Gall MA, Tarnow L et al (2007) Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes. Diabet Med 24:969–976PubMedCrossRef

10.

van Hecke MV, Dekker JM, Nijpels G et al (2005) Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study. Diabetologia 48:1300–1306PubMedCrossRef

11.

Forooghian F, Kertes PJ, Eng KT et al (2010) Alterations in the intraocular cytokine milieu after intravitreal bevacizumab. Invest Ophthalmol Vis Sci 51:2388–2392PubMedCentralPubMedCrossRef

12.

Puren AJ, Fantuzzi G, Dinarello CA (1999) Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1beta are differentially regulated in human blood mononuclear cells and mouse spleen cells. Proc Natl Acad Sci USA 96:2256–2261PubMedCentralPubMedCrossRef

13.

Skopinski P, Rogala E, Duda-Krol B et al (2005) Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. J Diabetes Complicat 19:335–338PubMedCrossRef

14.

Qiao H, Sonoda KH, Ikeda Y et al (2007) Interleukin-18 regulates pathological intraocular neovascularization. J Leukocyte Biol 81:1012–1021PubMedCrossRef

15.

Amin MA, Mansfield PJ, Pakozdi A et al (2007) Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways. Arth Rheum 56:1787–1797CrossRef

16.

Cho ML, Jung YO, Moon YM et al (2006) Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways. Immunol Lett 103:159–166PubMedCrossRef

17.

Chorostowska-Wynimko J, Skopinski P, Szaflik J et al (2005) In vitro angiomodulatory activity of sera from type 2 diabetic patients with background retinopathy. J Physiol Pharmacol 56(Suppl 4):65–70PubMed

18.

Hernandez C, Burgos R, Canton A et al (2001) Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case–control study. Diabetes Care 24:516–521PubMedCrossRef

19.

Burgos R, Simo R, Audi L et al (1997) Vitreous levels of vascular endothelial growth factor are not influenced by its serum concentrations in diabetic retinopathy. Diabetologia 40:1107–1109PubMedCrossRef

20.

Kuiper EJ, Van Nieuwenhoven FA, de Smet MD et al (2007) The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy. PloS One 3:e2675CrossRef

21.

Cui JZ, Chiu A, Maberley D et al (2007) Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy. Eye 21:200–208PubMedCrossRef

22.

Gerdes N, Sukhova GK, Libby P et al (2002) Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for atherogenesis. J Exp Med 195:245–257PubMedCentralPubMedCrossRef

23.

Takahashi HK, Iwagaki H, Hamano R et al (2007) Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated. Br J Pharmacol 150:816–822PubMedCentralPubMedCrossRef

24.

Canetti CA, Leung BP, Culshaw S et al (2003) IL-18 enhances collagen-induced arthritis by recruiting neutrophils via TNF-alpha and leukotriene B4. J Immunol 171:1009–1015PubMedCrossRef

25.

Aso Y, Okumura K, Takebayashi K et al (2003) Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes. Diabetes Care 26:2622–2627PubMedCrossRef

26.

Nakamura A, Shikata K, Hiramatsu M et al (2005) Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Care 28:2890–2895PubMedCrossRef

27.

Park CC, Morel JC, Amin MA et al (2001) Evidence of IL-18 as a novel angiogenic mediator. J Immunol 167:1644–1653PubMedCrossRef

Title: Increased intravitreous interleukin-18 correlated to vascular endothelial growth factor in patients with active proliferative diabetic retinopathy
Authors: Zongming Song
Min Sun
Fen Zhou
Fang Huang
Jia Qu
Ding Chen
Publication date: 01-08-2014
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 8/2014
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-014-2586-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Increased intravitreous interleukin-18 correlated to vascular endothelial growth factor in patients with active proliferative diabetic retinopathy

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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