Myocardial and plasma IL-18 levels were significantly elevated in patients with heart failure compared to controls, with higher plasma levels observed in patients who died during follow-up.
Observational (n=48)
Is the expression of IL-18 and its pathway components altered in patients with heart failure?
The IL-18 immunoinflammatory signaling pathway is altered in human heart failure and associated with mortality, suggesting a potential novel therapeutic target.
Interleukin (IL)-18 is the interferon-gamma-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-18Ralpha, 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-18Ralpha 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.
Mallat et al. (Wed,) conducted a observational in Heart failure (ischemic or dilated cardiomyopathy) (n=48). IL-18 pathway expression analysis vs. Controls was evaluated on Expression of IL-18, IL-18Ralpha, and IL-18BP in myocardial tissue and plasma IL-18 levels. Myocardial and plasma IL-18 levels were significantly elevated in patients with heart failure compared to controls, with higher plasma levels observed in patients who died during follow-up.
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