AIM: In patients, an association exists between pulmonary diseases and diastolic 
dysfunction of the left ventricle (LV). We have previously shown that alveolar 
hypoxia in mice induces LV diastolic dysfunction and that mice exposed to 
hypoxia have increased levels of circulating interleukin-18 (IL-18), suggesting 
involvement of IL-18 in development of diastolic dysfunction. IL-18 binding 
protein (IL-18BP) is a natural inhibitor of IL-18. In this study, we 
hypothesized that neutralization of IL-18 during alveolar hypoxia would improve 
LV diastolic function.
METHODS: Mice were exposed to 10% oxygen for 2 weeks while treated with IL-18BP 
or vehicle. Cardiac function and morphology were measured using 
echocardiography, intraventricular pressure measurements and magnetic resonance 
imaging (MRI). For characterization of molecular changes in the heart, both 
real-time PCR and Western blotting were performed. ELISA technique was used to 
measure levels of circulating cytokines.
RESULTS: As expected, exposure to hypoxia-induced LV diastolic dysfunction, as 
shown by prolonged time constant of isovolumic relaxation (τ). Improved 
relaxation with IL-18BP treatment was demonstrated by a significant reduction 
towards control τ values. Decreased levels of phosphorylated phospholamban 
(P-PLB) in hypoxia, but normalization by IL-18BP treatment suggest a role for 
IL-18 in regulation of calcium-handling proteins in hypoxia-induced diastolic 
dysfunction. In addition, MRI showed less increase in right ventricular (RV) 
wall thickness in IL-18BP-treated animals exposed to hypoxia, indicating an 
effect on RV hypertrophy.
CONCLUSION: Neutralization of IL-18 during alveolar hypoxia improves LV 
diastolic function and partly prevents RV hypertrophy.