title: Increased IL-6 levels are not related to NF-κB or HIF-1α transcription factors activity in the vitreous of proliferative diabetic retinopathy.
abstract: OBJECTIVE
  The purpose was to assess the activity of nuclear factor (NF)-κB and hypoxia inducible factor (HIF)-1α transcription factors and the expression levels of inflammation markers [interleukin (IL)-6 and IL-8] in the vitreous of patients suffering from proliferative diabetic retinopathy (PDR) scheduled for elective vitreous surgery in a single academic-based retina practice in a prospective clinical study.
  
  
  METHODS
  Twenty-seven patients with PDR were enrolled in the study. The severity of retinopathy was classified (0, 1, 2, 3, 4) and the activity of neovascularization was graded (0, 1, 2, 3, 4) by the surgeon intraoperatively. Samples of the vitreous were collected during surgery, and the activity of NF-κB and HIF-1α transcription factors and the expression levels of IL-6 and IL-8 were measured.
  
  
  RESULTS
  The majority of samples fell into the retinopathy class 3 (n = 12) or 4 (n = 13). The level of IL-6 increased from 68.9 ± 46.8 pg/ml to 102.7 ± 94.1 pg/ml, and IL-8 increased from 165.1 ± 136.0 pg/ml to 521.0 ± 870.9 pg/ml (mean ± S.D., nonsignificant change: normality test followed with Mann-Whitney Rank Sum Test). According to the neovascularization activity, the samples fell into grade 1 (n = 7), 2 (n = 12) or 3 (n = 7). In IL-6, there was a statistically significant increase (P < .05) from grade 2 to 3: 58.6 ± 40.3 pg/ml and 158.4 ± 102.5 pg/ml, respectively (Kruskal-Wallis One-Way Analysis of Variance on Ranks followed with Dunn's Method). The level of IL-8 was as follows: in grade 1: 118.0 ± 62.4 pg/ml, in grade 2: 192.3 ± 127.1 pg/ml and in grade 3: 884.3 ± 1161.0 pg/ml (statistically nonsignificant change). There was a statistically significant linear regression between IL-6 and IL-8 (P < .001): IL-6 = 51.88 pg/ml + (0.092*IL-8), r = 0.772. Increased activity of the NF-κB and HIF-1α transcription factors was not observed.
  
  
  CONCLUSIONS
  Interleukin-6 is a candidate to indicate activity of neovascularization process in PDR. It might be a new molecular therapeutic target to regulate innate immunity response in vitreous.
authors.affiliation: Department of Biology, University of Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Arjamaa
authors.forename: Matti
authors.initials: M
authors.lastname: Pöllönen
authors.forename: Kati
authors.initials: K
authors.lastname: Kinnunen
authors.forename: Tuomas
authors.initials: T
authors.lastname: Ryhänen
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D011446:Prospective Studies; D015861:Retinal Neovascularization / Q000209:etiology; D012720:Severity of Illness Index; D013223:Statistics as Topic; D018630:Vitreoretinopathy, Proliferative / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D014822:Vitreous Body / Q000378:metabolism* / Q000601:surgery
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B