Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy

Abstract

We measured interleukin-1 beta (IL-1b) and tumour necrosis factor-alpha (TNF-a) in the vitreous humour and serum of patients with proliferative diabetic retinopathy (PDR), in order to determine the role of these cytokines in the pathogenesis of the disease. Vitreous and serum samples were collected from 21 patients with PDR who were undergoing pars plana vitrectomy. Control vitreous samples were obtained from cadavers and control serum samples from healthy subjects. The cytokines were measured by enzymelinked immunosorbent assay. Vitreous IL-1b and TNF-a concentrations in patients with PDR exceeded those of controls (Po0.05), as did serum IL-1b and TNF-a. We suggest that increased vitreous IL-1b and TNF-a levels may play a significant role in the pathogenesis of PDR, which features abnormal cell proliferation and neovascularisation.

Fenofibric acid prevents retinal pigment epithelium disruption induced by interleukin-1β by suppressing AMP-activated protein kinase (AMPK) activation

“…Pro-inflammatory cytokines such as IL-1β play a crucial role in the pathogenesis of both PDR and DMO [19][20][21][22]. Apart from its intrinsic deleterious effect, IL-1β has been shown to stimulate several pro-inflammatory cytokines such as IL-6, IL-8 and monocyte chemotactic protein 1 (MCP-1) [26,27], which, in turn, have also been involved in both PDR and DMO [28][29][30].…”

“…In fact, treatment of RPE cells with either serum, interferon-γ, tumour necrosis factor-α, hepatocyte growth factor (HGF), IL-1β or placental growth factor-1 (PLGF-1) increases permeability and alters the levels or content of tight junction molecules [14][15][16][17][18]. As IL-1β plays an essential role in the development of DR [19][20][21][22], we decided to use this cytokine to provoke the breakdown of the RPE cell monolayer and to test the potential preventive effects of fenofibrate.…”

Management of diabetic retinopathy: could lipid-lowering be a worthwhile treatment modality?

“…These include inhibition of the VEGF pathway, 53 and sustained activation of the AMP-activated protein kinase pathway, which suggests a rationale for protection of endothelial cells in the retina against apoptosis. 54 Fenofibrate has also been shown to reduce the levels of pro-inflammatory cytokines, such as tumour necrosis factor-a, and interleukins, 55 which are elevated in patients with proliferative diabetic retinopathy, 56 to improve endothelium-dependent vascular reactivity 57 and reduce oxidative stress, 58 which have all been implicated in the progression of diabetic retinopathy. 9 Although the findings of the FIELD study are clearly of potential clinical interest, these need to be confirmed in other large prospective studies (such as ACCORD-EYE), and in an intention-to-treat study comparing fenofibrate with placebo with the primary endpoints of diabetic retinopathy.…”

Apoptosis and Inflammation Form the Mystery of Pathogenesis of Diabetic Retinopathy

“…Several studies have documented increased concentrations of cytokines, particularly vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and monocyte chemoattractant (MCP)-1 in the vitreous of patients with proliferative diabetic retinopathy and diabetic macular edema. [6][7][8][9][10] However, an inflammatory component was supported by the finding that vascular apoptosis was blocked by the systemic administration of antibody to Fas ligand, preventing leukostasis. 11 On the other hand, clearance of apoptotic cell prevents release of toxic contents from dying cells, promotes resolution of inflammation and produces growth factors that enhances macrophases clearance of apoptotic cells.…”