Role of vascular endothelial growth factor, interleukin-2 and tumor necrosis factor-alpha in diabetic retinopathy

Abstract

Background Diabetic retinopathy (DR) is a progressive vision-threatening complication of diabetes mellitus,but its pathogenic mechanism is still unclear. Recent studies showed that it may be associated with the inflammation response of retinal capillary. Cytokines can cause induction of proinflammatory and adhesion molecules and thereby increase monocyte endothelial cell adhesion, which is now accepted as the early key event in the development of DR. Objective The present study was to determine the relationship between the stages of DR and the levels of serum vascular endothelial growth factor (VEGF) , interleukin-2 ( IL-2 ), tumor necrosis factor-alpha (TNF-α) in diabetic patients. Methods This was a pilot case-controlled study. Ninety patients with type 2 diabetes mellitus were included in this clinical trial and 30 healthy individuals were enrolled as controls. The patients were grouped into the non-diabetic retinopathy(NDR) group,background DR group and proliferative DR(PDR) group according to the results from ophthalmoscopic examination and fundus fluorescein angiography(FFA) ,with 30 patients for each group. The levels of serum VEGF,IL-2,TNF-α were assayed by ELISA and compared among the 4 groups.Written informed consent was obtained from each subject before received any related medical examination to this study. Results The mean serum VEGF levels were(217.35±27. 87)ng/L,(298.31±49.26)ng/L,and(341.23±40. 18)ng/L, respectively, and mean serum IL-2 levels were( 12. 12± 1. 57 )ng/L, (16.43 ±2. 26 )ng/L, and (21.36±0. 86) ng/L,respectively and mean serum TNF-α levels were( 11.63±0. 94) ng/L, ( 17. 52±0. 65) ng/L,and(22. 01±0. 87 ) ng/L respectively in the patients with NDR ,background DR and PDR, showing significant differences from healthy controls with( 193.46±37. 39 ) ng/L for serum VEGF, ( 8. 99 ±0. 57 ) ng/L for serum IL-2 and ( 7.31 ±0. 52 ) ng/L for serum TNF-α ( F =126. 38, P＜0. 0 1 ;F =120. 37, P＜0. 01 ;F =99. 84, P＜0. 01 ). The levels of serum VEGF, IL-2, and TNF-α in the patients with the NDR,background DR and PDR were increased significantly. The level of serum VEGF showed the positively significant correlation with serum IL-2 level and TNF-α level ( r =0. 749, P ＜ 0.01 ; r =0. 631,P＜0. 01 ). The serum levels of VEGF, IL-2 and TNF-α showed a significantly positive correlation with the prolongation and severity of DR(r=0. 791 ,P＜0. 01 ;r=0. 665 ,P＜0. 01 ;r=0. 632,P＜0. 01 ). Conclusions VEGF, IL-2 and TNF-α play active roles in the generation and development of diabetic retinopathy, and the level of serum VEGF is closely associated with the levels of serum IL-2 and TNF-α. during the development of DR. Key words: Type 2 diabetes mellitus; Diabetic retinopathy; Vascular endothelial growth factor; Interleukin-2; Tumor necrosis factor-alpha