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Evidence for altered interleukin (IL)‐18 pathway in human heart failure
Author(s) -
Mallat Ziad,
Heymes Christophe,
Corbaz Anne,
Logeart Damien,
Alouani Sami,
CohenSolal Alain,
Seidler Tim,
Hasenfuss Gerd,
Chvatchko Yolande,
Shah Ajay M.,
Tedgui Alain
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2426fje
Subject(s) - heart failure , medicine , proinflammatory cytokine , ischemic cardiomyopathy , dilated cardiomyopathy , interleukin 18 , western blot , interleukin , pathophysiology , cardiology , cardiomyopathy , endogeny , endocrinology , inflammation , ejection fraction , cytokine , biology , biochemistry , gene
Interleukin (IL)‐18 is the interferon‐γ‐inducing factor and has potent proinflammatory activities. IL‐18 has been recently implicated in atherosclerotic plaque instability and myocardial ischemia‐reperfusion injury. However, it is unknown whether IL‐18 expression is increased in human myocardium or if it has any role in heart failure. We analyzed the expression of IL‐18, its receptor IL‐18Rα, and its endogenous inhibitor, IL‐18 binding protein (IL‐18BP) in myocardial tissue from patients with end‐stage heart failure (ischemic or dilated cardiomyopathy) and controls by use of quantitative real‐time reverse transcriptase polymerase chain reaction, Western blot or immunohistochemical techniques. Plasma levels of IL‐18 were also determined in 48 patients with heart failure. IL‐18 mRNA and protein levels were up‐regulated in the myocardium of patients with ischemic cardiomyopathy. Both ischemic and dilated myocardium showed increased IL‐18Rα levels, suggesting potential biological effects. In addition, mRNA levels of IL‐18 BP were down‐regulated in the failing myocardium. Finally, plasma IL‐18 levels were significantly elevated in patients with heart failure and were higher in those who died at follow‐up than in survivors. The results suggest a potential role for the immunoinflammatory IL‐18 signaling pathway in the pathophysiology of heart failure and identify novel therapeutic targets for future testing.