Authors: Abeywardena, Mahinda Y.; Leifert, Wayne R.; Warnes, Kirsty E.; Varghese, Jose N.; Head, Richard J.

Source: Current Pharmaceutical Design, Volume 15, Number 15, May 2009 , pp. 1809-1821(13)

Publisher: Bentham Science Publishers

Abstract:

Interleukin-6 (IL-6) is a multifunctional pro-inflammatory cytokine that is tightly regulated and expressed at low levels in healthy individuals. Increased IL-6 expression has been associated with a variety of diseases, including inflammatory conditions such as atherosclerosis and cardiovascular disease (obesity, myocardial infarction and type II diabetes). Cytokines including IL-6 and tumour necrosis factor alpha as well as acute phase proteins such as C-reactive protein (CRP) and fibrinogen are key biochemical risk factors for the development of these disease conditions. IL-6 is the key cytokine responsible for the stimulus of synthesis and secretion of CRP.

IL-6 activates cell surface signalling via the assembly of IL-6, the IL-6 receptor (IL-6R) and the signalling receptor gp130. Assembly of the (hexameric) signalling complex of IL-6, IL-6R and gp130 occurs in a sequential manner and therefore this signalling complex lends itself to several potential sites for drug targeting. This review discusses some of the mechanisms of IL-6 signalling on various aspects of cardiovascular biology as well as some recent developments in drug targeting of this complex.

Keywords: Interleukin-6; inflammation; cardiovascular disease; endothelium; C-reactive protein; insulin resistance

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209788186290

Affiliations: 1: CSIRO Human Nutrition, PO Box 10041, Adelaide BC, SA 5000, Australia.

Publication date: 2009-05-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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