Cardiovascular biology of interleukin-6.
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.
CSIRO Human Nutrition, Kintore Avenue, Adelaide, South Australia 5000, Australia. mahinda.abeywardena@csiro.au
Mahinda Y
MY
Abeywardena
Wayne R
WR
Leifert
Kirsty E
KE
Warnes
Jose N
JN
Varghese
Richard J
RJ
Head
D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015398:Signal Transduction; D000093242:Interleukin-6 Inhibitors
D002097:C-Reactive Protein; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors