Altered interleukin-1 receptor antagonist and interleukin-18 mRNA expression in myocardial tissues of patients with dilatated cardiomyopathy

Abstract

Interleukin-1 (IL-1) is a potent regulator of cell proliferation, inflammation, and contraction of cardiovascular cells. It has been proposed that the IL-1/IL-1ra (IL-1 receptor antagonist) ratio influences these functions. Other members of the IL-1 family and the related caspase-1 also contribute to regulation of IL-1-mediated functions. We determined the mRNA expression of caspase-1, caspase-3, IL-1α, IL-1β, IL-18, IL-1 receptor type I (IL-1-RI), and IL-1ra in left ventricle tissue of hearts from patients with ischemic or dilated cardiomyopathy (ICM or DCM) and in control tissues from unused donor transplant hearts in RT-PCR experiments. We show that the expression of caspase-1, caspase-3, IL-1β, and IL-1-RI mRNA was not different between patients and control tissues. Furthermore, we did not find detectable amounts of IL-1α mRNA in any of these adult myocardial tissues. On the other hand, expression of IL-18 RNA was lower in myocardium of both patient groups compared with control hearts. Furthermore, IL-1ra mRNA expression was significantly lower in tissues of DCM patients compared with ICM patients and controls. This was in line with a trend towards lower IL-1ra protein levels in myocardial tissues of DCM patients. In contrast with the adult tissues discussed above, which did not express IL-1α mRNA, commercially available human fetal tissue expressed IL-1α mRNA. On the other hand IL-1β mRNA was present in fetal and in adult human heart tissue. Our data provide evidence for an altered ratio of IL-1/IL-1ra in DCM patients. This dysregulation may contribute to pathogenesis and/or progression of heart disease by modulating the otherwise balanced IL-1-mediated functions in cardiovascular cells.