Endotoxin-activated cultured neonatal rat cardiomyocytes express functional surface-associated interleukin-1 alpha

lnterleukin-1 (IL-1) is a potent regulator of cardiovascular proliferation, apoptosis, contraction or production of inflammatory mediators. Thus, we investigated expression and function of IL-1 in cultured neonatal rat heart cells upon endotoxin stimulation. We show that cultured neonatal rat cardiomyocytes expressed IL-1 alpha and IL-1 beta mRNA. The cells expressed functional cell-associated IL-1 activity and a specific anti-IL-1 alpha-antibody inhibited the activity. Biologically active IL-la was present at the cell surface of the cardiomyocytes, as indicated in co-culture experiments. Immunohistochemistry showed IL- 1 alpha-staining of the neonatal cardiomyocytes. Although the cells also expressed IL-1 alpha mRNA, we did not detect IL-1 beta in the supernatants of cultured cardiomyocytes by ELISA or in immunohistochemical staining. Furthermore, neonatal and adult rat heart tissues expressed IL-1 alpha mRNA, whereas fetal, but not adult, human cardiac tissues expressed detectable IL-1 alpha mRNA. In contrast, IL-1 beta mRNA was present in rat and human fetal and adult samples. Furthermore, in patients with dilated or ischemic cardiomyopathy, we measured IL-1 beta, but not IL-1 alpha, mRNA. These results provide evidence for the presence of functionally active IL-1 alpha on the cell surface of neonatal rat cardiomyocytes and may suggest a differential role of IL-1 alpha in regulation of cellular functions during development, aging and disease in rat and human heart cells.