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. (2004) conducted an 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.