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Home/Research/Paper Chase/Endothelial cell activation and high interleukin-1 secretion in the pathogenesis of acute Kawasaki disease.
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
To investigate the pathogenesis of Kawasaki disease, the effects of intravenous gammaglobulin treatment on circulating cytotoxic antibodies against endothelial cells, in-situ endothelial cell activation, and cytokine production and action were examined. Gammaglobulin treatment did not reduce cytotoxic antibody activity against endothelial cells in six patients tested. Expression of endothelial cell activation antigens (endothelial-leucocyte adhesion molecule-1 [ELAM-1] and intercellular adhesion molecule-1) was detected by means of immunoperoxidase staining in skin biopsy samples from five patients before treatment. Samples were obtained immediately after treatment from six patients; there was no endothelial cell activation in four and the two with persistent activation had persistent fever and mucocutaneous symptoms. Peripheral blood mononuclear cells from ten of sixteen acute Kawasaki disease patients spontaneously secreted high levels of interleukin-1 (IL-1). IL-1 secretion remained high in four gammaglobulin-treated patients in whom coronary artery abnormalities developed but fell to normal in six treated patients who had no coronary artery abnormalities. In cell culture, gamma globulin did not inhibit endothelial cell expression of ELAM-1 in response to IL-1 or tumour necrosis factor. The association between improvement of clinical symptoms and the reduction of cytokine secretion and reversal of endothelial cell activation supports a role for immune-mediated injury to cytokine-induced endothelial cell antigens in the pathogenesis of this disorder.