Interleukin 18 in the heart.
IL-18, originally termed as interferon gamma (IFN-gamma) inducing factor, is a proinflammatory cytokine that belongs to the IL-1 cytokine superfamily. IL-18 plays an important role in immune, infectious, and inflammatory diseases due to its induction of IFN-gamma. However, accumulated evidence has demonstrated that other effects of IL-18 are independent of IFN-gamma. Here, we reviewed the current literatures regarding the role of IL-18 in the heart and cardiovascular system. Infiltrated neutrophils, resident macrophages, endothelial cells, smooth muscle cells, and cardiomyocytes in the heart are able to produce IL-18 in response to injury. IL-18 is produced as a biologically inactive precursor (pro-IL-18) that is activated by caspase 1 (the IL-1beta converting enzyme). Elevated IL-18 levels have been observed in cardiac tissue and circulation after myocardial I/R and sepsis. The possible cellular and molecular mechanisms concerning IL-18-induced myocardial injury include induction of inflammation, increased apoptosis, a cardiac hypertrophy effect, modulation of mitogen activated protein kinase activation, and changes in intracellular calcium. Finally, we briefly reviewed the therapeutic strategies for inhibiting IL-18's biological activity to protect cardiac tissue from injury.
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Meijing
M
Wang
Troy A
TA
Markel
Daniel R
DR
Meldrum
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced; D004789:Enzyme Activation; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D020382:Interleukin-18 / Q000097:blood / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015398:Signal Transduction
D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium