Ischemic heart disease is a widespread cause of death. During infarction, myocardial injury is mediated by release of several pro-inflammatory cytokines including multifunctional Interleukin-1 (IL-1). In various tissues, IL-1-mediated deleterious effects are known to be attenuated via the over-expression of natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra). In the present investigation, IL-1ra distribution in healthy and infarcted myocardium was studied by light and electron microscopy. Immunohistochemically, cardiomyocyte positivity was found for normal myocardium as well as its increasing in infarction border areas and ischemic ones. In addition, extracellular matrix and intravascular plasma exhibited reactivity for this cytochine in ischemic areas. Immunogold labelling provided further details on intracytoplasmatic and extracellular distribution. In particular, prominent gold particle distribution appeared on intercalated discs of normal and hypertrophic cardiomyocytes as well as on thickened Z-lines in these latter. The present results suggest that cardiomyocytes represent a major source of IL-1ra, even though additional contribution by blood derived citochine is to be taken in account in ischemic areas. The first evidence is also provided of an in vivo IL-1ra production by cardiomyocytes naturally occurring in human myocardium and its infarctions associated increase, consistently with a cardioprotective role.
