Tumor necrosis factor-alpha is expressed by monocytes/macrophages following cardiac microembolization and is antagonized by cyclosporine

Abstract

The time course of expression of TNF-α in myocardial wound healing following ischemic injury was investigated in the porcine heart. Microembolization was used to induce focal ischemia and necrosis in hearts of 39 adult pigs. The animals were sacrified after 3, 6, 12, 24 h, 3 and 7 days, and after 4 weeks, and the myocardial tissue was studied by immunofluorescence using specific antibodies. TNF-α containing cells were identified as monocytes/macrophages by double staining with a muramidase antibody. Monocytes/macrophages were the only source of TNF-α. Microembolization caused multiple necrotic foci with loss of myocytes in the left ventricular myocardium. These foci contained numerous monocytes/macrophages and showed an inflammatory reaction typical of wound healing followed by replacement with scar tissue. The number of TNF-α positive cells increased after 24 h, peaked between 3–7 days and slowly decreased thereafter. Expression of TNF-α in monocytes/macrophages was significantly reduced after pretreatment of pigs with cyclosporine or dexamethasone. It is concluded that 1.) in myocardial tissue monocytes/macrophages are the only cell type expressing TNF-α, 2.) TNF-α is involved in wound healing after ischemia, and 3.) synthesis of TNF-α and inflammatory angiogenesis can be inhibited be treatment with either cyclosporine or dexamethasone.