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Evidence for the regulation of levels of plasma adhesion molecules by proinflammatory cytokines and their soluble receptors in type 1 diabetes
Author(s) -
MohamedAli V.,
Armstrong L.,
Clarke D.,
Bolton C. H.,
Pinkney J. H.
Publication year - 2001
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1046/j.1365-2796.2001.00900.x
Subject(s) - proinflammatory cytokine , medicine , endocrinology , receptor , cell adhesion molecule , cytokine , tumor necrosis factor alpha , intercellular adhesion molecule 1 , von willebrand factor , soluble cell adhesion molecules , diabetes mellitus , immunology , inflammation , cell adhesion , adhesion , chemistry , platelet , organic chemistry
. Mohamed‐Ali V, Armstrong L, Clarke D, Bolton CH, Pinkney JH (University College London Medical School, Whittington Hospital, London; University Department of Medicine, Southmead Hospital, Bristol; and Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK). Evidence for the regulation of levels of plasma adhesion molecules by proinflammatory cytokines and their soluble receptors in type 1 diabetes. J Intern Med 2001; 250: 415–421. Objectives. To investigate the regulation of soluble adhesion molecules by tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), and relationships with circulating cytokine receptors, in vivo , in type 1 diabetes. Design. Cross‐sectional study. Setting. University hospital diabetes clinic. Subjects. A total of 47 non‐nephropathic, Caucasian type 1 diabetics and 39 nondiabetic controls. Outcome measures. Plasma levels of TNF‐α, IL‐6, their soluble receptors and adhesion molecules intercellular adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), sE‐selectin and von Willebrand factor (vWF), and risk factors for cardiovascular disease. Results. Plasma concentrations of IL‐6 were elevated in diabetic patients compared with controls [median (interquartiles) 1.28 (0.89–2.65) vs. 0.66 (0.45–1.73) pg mL −1 : P =0.016], and in these patients IL‐6 and soluble IL‐6 receptor (sIL‐6R) levels correlated with concentrations of sICAM‐1 ( r =0.41, P =0.012 and r =0.31, P =0.04, respectively). Tumour necrosis factor‐α soluble receptor‐2 (sTNFRII), but not TNF‐α or tumour necrosis factor soluble receptor‐1 (sTNFRI), was elevated in diabetic subjects ( P =0.027). Plasma TNF‐α levels correlated with sVCAM‐1 ( r =0.39, P =0.008), triglycerides ( r =0.36, P =0.021) and diastolic blood pressure ( r =0.35; P =0.024). Both sTNFRI and sTNFRII correlated with blood pressure ( r =0.46, P =0.002; r =0.32, P =0.034) and triglycerides ( r =0.33, P =0.033; r =0.29, P =0.05). In contrast, HDL‐cholesterol and triglyceride were related to sE‐selectin ( r =−0.45 and +0.45; both P < 0.001). Neither sE‐selectin nor vWF were related to cytokine concentrations. Finally, both TNF‐α and sIL‐6R correlated sTNFRI and RII ( r =0.44–0.49, P < 0.001). None of these interactions were apparent in control subjects. Conclusions. (i) IL‐6, through effects on sICAM‐1, and TNF‐α via effects on sVCAM‐1, may promote vascular adhesion; (ii) plasma levels of TNF‐α are associated with dyslipidaemia and increased blood pressure, adding to vascular disease risk; (iii) the actions of both cytokines are probably modified by altered production of soluble receptors in diabetic subjects.