Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients

PLoS One. 2015 Sep 9;10(9):e0137358. doi: 10.1371/journal.pone.0137358. eCollection 2015.


Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM), 26 patients with idiopathic macular hole (MH), and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / blood
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / immunology
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / surgery
  • Eye / metabolism
  • Eye / pathology
  • Female
  • Humans
  • Immunity, Innate*
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation / surgery
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Retinal Perforations / metabolism
  • Retinal Perforations / pathology
  • Sarcoidosis / immunology
  • Sarcoidosis / metabolism
  • Sarcoidosis / pathology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Th2 Cells / metabolism
  • Th2 Cells / pathology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Uveitis / metabolism
  • Uveitis / pathology
  • Vitrectomy
  • Vitreous Body / immunology
  • Vitreous Body / metabolism
  • Vitreous Body / pathology


  • Cytokines
  • TNF protein, human
  • Tumor Necrosis Factor-alpha

Grant support

The authors have no support or funding to report.