Review articleInflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?☆
Section snippets
Inflammation, infection and coronary heart disease
Inflammation leads to the localised recruitment of neutrophils and monocytes, and the presence of activated macrophages in the cap of the atherosclerotic plaque [1] has led to suggestions that they contribute to plaque rupture through effects on matrix metalloproteinases [2]. Pathological and intervention studies have implicated organisms like Chlamydia in initiating or maintaining such inflammation [3], [4], but there is also evidence that elevated concentrations of the acute phase reactant,
How could IL-6 increase atherothrombotic risk?
IL-6 might play a key role in the development of coronary disease through a number of different mechanisms; metabolic, endothelial and coagulant. IL-6 increases basal glucose uptake, alters insulin sensitivity, increases the release of adhesion molecules by the endothelium and increases the hepatic release of fibrinogen, as well as having procoagulant effects on platelets. There is a close relationship between circulating concentrations of CRP, IL-6 and TNF-α, with the components of the insulin
Obesity, adipose tissue and IL-6
Recent observations from our laboratory have suggested a previously unsuspected source for this cytokine. Using the method of arteriovenous difference measures across a subcutaneous adipose tissue bed and radio-xenon estimates of adipose tissue blood flow, net IL-6 production by human subcutaneous adipose tissue has been demonstrated in vivo [32]. In healthy men and women the production of IL-6, as well as systemic concentrations, increase with adiposity and we have estimated that as much as a
Testing the IL-6 hypothesis
The paradigm shown in Fig. 1 suggests a number of possible experiments to test specific parts of the overall scheme. However, because of the time scale of the evolution of atherothrombotic disease it is more problematic to test the role of IL-6 in CHD directly. Any test of the role of IL-6 will require other evidence, such as from animal models with overexpression or knockout of the IL-6 gene, or from the use of monoclonal antibodies or antagonists. Ultimately, prospective studies will be
Acknowledgements
The work outlined in this article has been supported by grants from the Medical Research Council, the British Heart Foundation (RG95007; SP/98003), the Wellcome Trust, the British Diabetic Association, the Sir Jules Thorn Charitable Trust (97/18A), the National Institute of Ageing, and Biomed 2.
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Cited by (0)
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On behalf of the University College London Interleukin-6 Group. Additional membership: Dr Simon Coppack, Professor Patrick Vallance, Professor John Martin, Professor Michael Marmot, Dr Eric Brunner and Louise Flower.