title: Serum inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF have influence on the development of diabetic retinopathy.
abstract: OBJECTIVE
  The aim of this study was to analyze the correlation between serum levels of inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM).
  
  
  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-1beta, IL-6, TNF-alpha 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-1beta, IL-6, TNF-alpha 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-1beta (p = 0.01) and IL-6 (p = 0.029) and elevated TNF-alpha 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-1beta (p = 0.003), TNF-alpha (p = 0.002) and VEGF (p = 0.005) between the different subgroups. Patients with proliferative DR showed significantly higher values of serum IL-1beta (p < 0.0001), IL-6 (p = 0.007), TNF-alpha (p = 0.002) and VEGF (p < 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-1beta, p = 0.045), and hyperlipidemia (except for TNF-alpha, p = 0.05). TNF-alpha(p = 0.05) and VEGF (p = 0.047) serum levels correlated with the levels of glycosylated hemoglobin, and IL-1beta, TNF-alpha and VEGF correlated with the general indicators of inflammation (ESR and fibrinogen).
  
  
  CONCLUSIONS
  Serum concentrations of IL-1beta, TNF-alpha 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.
authors.affiliation: Department of Ophthalmology, St. George University Hospital, Medical University, Plovdiv, Bulgaria.
authors.forename: Desislava N
authors.initials: DN
authors.lastname: Koleva-Georgieva
authors.forename: Nelly P
authors.initials: NP
authors.lastname: Sivkova
authors.forename: Dora
authors.initials: D
authors.lastname: Terzieva
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003930:Diabetic Retinopathy / Q000097:blood / Q000209:etiology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A