Serum inflammatory cytokines IL-1β, IL-6, TNF-α and VEGF have influence on the development of diabetic retinopathy

Abstract

AIm: The aim of this study was to analyze the correlation between serum levels of inflammatory cytokines Il-1β, Il-6, TnF-α and vegF and the presence and severity of diabetic retinopathy (dR) in patients with type 2 diabetes mellitus (dM). PAtIents And methods: In this prospective study we included 38 healthy volunteers (group 1) and 39 patients with type 2 dM (group 2). all participants underwent routine ophthalmological examination and laboratory analysis of the serum cytokines Il-1β, Il-6, TnF-α and vegF. group 2 patients were additionally examined by colour fundus photography and fluorescein angiography to determine the dR stage. We studied the correlation of Il-1β, Il-6, TnF-α and vegF with the presence of dM, the presence and severity of dR, the duration of dM and dR, the serum levels of glycosylated haemoglobin, as well as with hyperlipidemia and the general indicators of inflammation -erythrocyte sedimentation rate (eSR) and fibrinogen. results: The group 2 patients had statistically significantly higher levels of Il-1β (р = 0.01) and Il-6 (р = 0.029) and elevated TnF-α and vegF levels in comparison with group 1 patients. group 2 patients were divided into 5 subgroups depending on the severity of dR: patients without dR (n = 11), patients with mild non-proliferative dR (n = 10), patients with moderate non-proliferative dR (n = 5), and patients with severe non-proliferative dR (n = 2) (total number of non-proliferative dR (n = 17)) and patients with proliferative dR (n = 11). The comparative analysis showed statistically significant differences in the serum levels of Il-1β (р = 0.003), TnF-α (р = 0.002) and vegF (р = 0.005) between the different subgroups. Patients with proliferative dR showed significantly higher values of serum Il-1β (р < 0.0001), Il-6 (р = 0.007), TnF-α (р = 0.002) and vegF (р < 0.0001) compared with the patients with non-proliferative dR. The cytokine serum levels did not correlate with the duration of dM, the duration of dR (except for Il-1β, р = 0.045), and hyperlipidemia (except for TnF-α, р = 0.05). TnF-α (р = 0.05) and vegF (р = 0.047) serum levels correlated with the levels of glycosylated hemoglobin, and Il-1β, TnF-α and vegF correlated with the general indicators of inflammation (eSR and fibrinogen). conclusIon: Serum concentrations of Il-1β, TnF-α and vegF have an effect on the development and progression of dR. They correlate with the presence and severity of the disease. Whether serum cytokines can play the role of a prognostic factor or serve as a means to choose a proper therapeutic agent for the treatment of diabetic retinopathy should be analyzed by further more extensive prospective longitudinal studies in future. key words: diabetic retinopathy, cytokines, interleukins, tumor necrosis factor-α, vascular endothelial growth factor abbreviations useD in the stuDy:

Immunological Risk Factors for the Development and Progression of Diabetic Retinopathy

“…TNF-may become a relevant indicator of development and risk of diabetic retinopathy. Similar observations were made in adult patients with PDR (Gustavsson et al, 2008;Koleva-Georgieva et al, 2011). Levels of TNF-in vitreous of Type 2 diabetic patients with PDR were higher than those found in control group.…”

“…On the other hand M1 macrophages prevented neovascularisation within retina due to high secretion of IL-6, IL-12 and IL-23. Although, majority of reports confirm its negative role in the onset and progression of diabetic retinopathy (Noma et al, 2009;Funk M et al, 2010;Koleva-Georgieva et al, 2011). IL-6 is produced mainly by macrophages, monocytes, lymphocytes T and B, while in the eye IL-6 is produced by keratocytes, Müller cells, pigmented epithelium, corneal epithelium, iris and ciliary body (Yoshida et al, 2001).…”

Angiogenic Factors and Cytokines in Diabetic Retinopathy

“…Alternatively, TNF-α knockout may block DR progression by removing TNF-α from the bloodstream. It is feasible that TNF-α represents an external factor that promotes or aggravates retinal inflammation and vascular dysfunction in DR. Several clinical studies have found that average serum levels of TNF-α are increased in patients with PDR and correlate with other systemic indicators of inflammation [85,87,[149][150][151][152][153]. Relative to healthy controls, plasma levels of TNF-α progressively increase in diabetic patients with no retinopathy, with nonproliferative DR and with PDR [153].…”

Transformujący czynnik wzrostu β1 (TGFβ1) i naczyniowo-śródbłonkowy czynnik wzrostu (VEGF) we krwi ludzi zdrowych i chorych z orbitopatią Gravesa — nowy mechanizm działania glikokortykosteroidów?

“…Disease processes which have been shown to increase vascularity include, in particular, endocrine glands illness [24,25], acromegaly [19], pituitary adenomas [26,27], autoimmune thyroid disease, goitre, neoplasms [18,22] and eye disorders -retinopathy occurring in premature infants [18,28], diabetic retinopathy [18,20,21,[29][30][31], uveitis and other ocular illnesses. Angiogenesis commonly occurs in inflammatory diseases [18-20, 22, 24-27].…”