Original articleInflammatory cytokines in vitreous fluid and serum of patients with diabetic vitreoretinopathy
Introduction
Proliferative diabetic retinopathy is associated with elevated intravitreous concentrations of certain cytokines. Although inflammatory cytokines are considered to play an important role in the pathogenesis of diabetic retinopathy (Feigold & Grunfeld, 1992), precise mechanisms are not yet fully understood. Inflammatory cytokines include interleukin-6, 8 (IL-6, 8) and tumor necrosis factor (TNF)-α. We analyzed vitreous fluid and serum samples taken from patients with diabetic retinopathy for these cytokines using a sensitive enzyme-linked immunosorbent assay (ELISA).
IL-6 is a cytokine with a variety of biologic activities including the ability to activate macrophages. IL-8 regulates and activates neutrophils in acute inflammation Feigold & Grunfeld, 1992, Huber et al., 1991, Ida et al., 1992. TNF-α has previously been associated with the acute phase response being produced by macrophages in response to endotoxemia, inflammation, and cancer (Spiegelman & Hotamisligil, 1993).
The objective of this pilot study was to investigate the potential value of inflammatory cytokines measurements in serum for detecting diabetic retinopathy, as well as the pathogenetic significance of these cytokines in vitreous fluid.
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Patients
We assayed vitreous samples and sera from 47 patients with proliferative retinopathy as well as 21 patients with noninflammatory retinopathies including macular holes. After informed consent was obtained, vitreous fluid samples (200 to 700 μl) were collected at therapeutic vitrectomy. Serum was separated from blood samples by clotting and centrifugation. Vitreous and serum samples were stored at −20°C. Both groups of samples were collected between 1996 and 1999. Nonretinopathy control samples
Results
Vitreous concentration of IL-6 were 64.7±12.8 pg/ml in proliferative retinopathy, much greater levels in noninflammatory retinopathy (12.8±4.5 pg/ml, P<.005). Vitreous concentration of IL-8 in vitreous also was greater in proliferative retinopathy than in noninflammatory retinopathy (34.0±11.5 vs. 6.1±2.0 pg/ml, P<.005). TNF-α concentration were not statistically different in proliferative retinopathy from those in noninflammatory retinopathy (0.10±0.001 vs. 0.11±0.002 pg/ml) (Fig. 1).
Serum
Discussion
This report showed that IL-6 and IL-8 were significantly increased in vitreous fluid in patients with proliferative diabetic retinopathy, while neither serum cytokine was increased. An opposite pattern characteristic for TNF-α was decidedly higher in proliferative retinopathy than in various noninflammatory retinopathies serum concentration. The results suggest that inflammatory cytokines may be pathogenically important in the proliferative vitreoretinopathy of diabetes.
IL-8, a mediator of host
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