Evidence for control of tumour necrosis factor‐alpha (TNF‐α) activity by TNF receptors in patients with proliferative diabetic retinopathy

• Published in: Clinical and experimental immunology Vol. 115; no. 3; pp. 409 - 414
• Main Authors: LIMB, G. A, SOOMRO, H, JANIKOUN, S, HOLLIFIELD, R. D, SHILLING, J
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.03.1999; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; Antigens, CD - blood; Associated diseases and complications; Biological and medical sciences; Case-Control Studies; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Diabetic Retinopathy - blood; Diabetic Retinopathy - etiology; Diabetic Retinopathy - immunology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Humans; In Vitro Techniques; insulin‐dependent diabetes mellitus; Leukocytes, Mononuclear - immunology; Lipopolysaccharides - pharmacology; Male; Medical sciences; Middle Aged; Original; PDR; Receptors, Tumor Necrosis Factor - blood; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; sTNF‐R; Tumor Necrosis Factor-alpha - biosynthesis; tumour necrosis factor; Endocrinopathy; Human; Immunopathology; Retinopathy; Pathogenesis; Cytokine; Autoimmune disease; Vascular disease; Eye disease; Insulin dependent diabetes; Complication; Neovascularization; Tumor necrosis factor α; Biological receptor
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1999.00839.x

TNF‐α has been implicated in the pathogenesis of insulin‐ dependent diabetes mellitus (IDDM). At present there are no studies linking serum levels of soluble TNF receptors (sTNF‐R) to the development of diabetic microvascular complications such as proliferative diabetic retinopathy (PDR), or to the production of TNF‐α in these patients. We investigated serum levels of sTNF receptors (sTNF‐RI and sTNF‐RII) in IDDM patients with or without PDR, and related these to the in vitro production of TNF‐α upon activation of whole blood and isolated mononuclear cells (MNC). We observed higher serum levels of sTNF‐RI in IDDM patients with active (range 945–6630 pg/ml; P = 0.029) or quiescent PDR (range 1675–4970 pg/ml; P = 0.00092) than in individuals with IDDM without retinopathy (range 657–2617 pg/ml) or healthy controls (range 710–1819 pg/ml; P = 0.0092 and 0.0023, respectively). Increased serum levels of sTNF‐RII were also seen in IDDM patients with active PDR (range 1749–5218 pg/ml; P = 0.034) or quiescent PDR (range 1494–5249 pg/ml; P = 0.0084) when compared with disease controls (range 1259–4210 pg/ml) or healthy subjects (range 1237–4283 pg/ml). Whole blood production of biologically active TNF‐α was lower in PDR patients than in disease (P = 0.04) and healthy controls (P < 0.005), contrasting with a higher production of TNF‐α by lipopolysaccharide (LPS)‐activated MNC from PDR patients (P = 0.013). Inhibition of TNF‐α by TNF‐R in plasma supernatants of activated blood from PDR patients was demonstrated by increase of TNF‐α activity in the presence of anti‐TNF‐RI and anti‐TNF‐RII antibodies. These observations suggest that abnormalities in TNF‐α production and control may operate during the development of microvascular complications of diabetes mellitus.