Pro-inflammatory cytokine profile is present in the serum of Mexican patients with different stages of diabetic retinopathy secondary to type 2 diabetes

Abstract

AimIt’s been reported that pro-inflammatory cytokines are elevated in patients with diabetic retinopathy (DR); this may contribute to the pathophysiology of the disease. The aim of this study is to measure the concentration of various inflammatory cytokines from the main CD4+ T helper inflammatory responses in blood serum from Mexican patients with DR in different stages using cytometric bead array (CBA) technology and correlate them with the presence and severity of DR in order to find possible DR biomarkers that serve as diagnostic or therapeutic predictors.Methods64 subjects were included in the study, 16 in the control group, 16 in the type 2 diabetes mellitus no DR (NDR) group, 16 in the non-proliferative DR (NPDR) group and 16 in the proliferative DR (PDR) group. Cytokine concentrations of interleukin (IL) 1ß, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, IL‐17A, tumour necrosis factor alpha (TNFα) and interferon-gamma in serum samples were measured using Human Inflammatory and TH1/TH2/TH17 CBA Kit.ResultsIL-6, IL-12, IL-17a and TNFα were significantly higher in the patients with DR compared with the control group. The PDR group showed a slightly lower concentration of serum cytokines IL-6, IL-12 and IL-17a. TNFα showed a higher concentration compared with healthy controls, NDR and NPDR subjects. We also found a positive statistical correlation between the presence and severity of DR with the clinical parameters haemoglobin A1c, body mass index and serum creatinine and the concentration of serum cytokines IL-6 and TNFα.ConclusionOur findings suggest that patients with diabetes and DR have a stronger chronic inflammatory profile compared with non-diabetic subjects.

Correlation between the progression of diabetic retinopathy and inflammasome biomarkers in vitreous and serum – a systematic review

“…Of the 20 eligible studies, 19 were cross-sectional case–control [ 39 – 58 ] and one was longitudinal [ 59 ]. In total, eight studies [ 40 , 43 , 44 , 50 , 52 , 53 , 55 , 57 ] graded DR severity using the International Clinical Diabetic Retinopathy Disease Severity Scale (ICDRDSS), four [ 46 , 48 , 49 , 54 ] used the Early Treatment Diabetic Retinopathy Study Scale (ETDRSS), five [ 39 , 45 , 47 , 51 , 59 ] relied on the ophthalmologists and the remaining three studies [ 41 , 42 , 58 ] did not report the grading method (Table S 4 ). T2DM patients were grouped according to the DR severity level: no DR (NDR), non-proliferative DR (NPDR) and proliferative DR (PDR).…”

“…Moreover, different assays were employed to measure the biomarker levels in serum and vitreous. For studies only using one biomarker detection assay, 10 [ 39 , 42 , 43 , 45 , 47 , 48 , 50 , 52 , 57 , 58 ] employed enzyme-linked immunosorbent assay (ELISA), three [ 44 , 53 , 55 ] used a Luminex magnetic assay, two [ 41 , 54 ] performed cytometric bead array (CBA), and two [ 46 , 49 ] utilized a chemiluminescent immunometric assay (Table S 4 ). Furthermore, three studies [ 40 , 51 , 59 ] used two assays to detect different biomarkers (Table S 4 ).…”

“…Overall, studies found a significant increase in pro-inflammatory biomarkers in both the vitreous and serum of patients with PDR compared to controls, with IL-6 and TNF-α being the most studied biomarkers (Table 2 ). In total, 10 serum pro-inflammatory biomarkers increased significantly in PDR relative to NPDR (IL-6: [ 40 , 41 , 44 ], TNF-α: [ 46 , 48 , 51 , 54 ], CRP: [ 51 ], NO: [ 46 ] IL-2R: [ 46 ], sIL-6R: [ 44 ], IL-12: [ 47 ], VEGF: [ 48 , 51 ]) IL-1β: [ 48 ], IL-18: [ 47 ]).…”

“…In total, 10 serum pro-inflammatory biomarkers increased significantly in PDR relative to NPDR (IL-6: [ 40 , 41 , 44 ], TNF-α: [ 46 , 48 , 51 , 54 ], CRP: [ 51 ], NO: [ 46 ] IL-2R: [ 46 ], sIL-6R: [ 44 ], IL-12: [ 47 ], VEGF: [ 48 , 51 ]) IL-1β: [ 48 ], IL-18: [ 47 ]).…”

Retinal transcriptome and cellular landscape in relation to the progression of diabetic retinopathy

“…32 Increasing evidence demonstrates that inflammation is crucial to the development of DR. Increased level of a variety of inflammatory cytokines and chemokines were observed in serum 33 and ocular samples (aqueous and vitreous) from patients with PDR. 34 However, it remains unclear how inflammation involves in the progression of DR and its relationship with the severity of DR due to the difficulty of sample collection.…”