Elevated circulating tumor necrosis factor-alpha in patients with Kawasaki disease.

The mechanism of vascular injury in Kawasaki disease (KD) is unclear. Recent studies suggest a role for circulating antibodies that are cytotoxic for endothelial cell antigens inducible by cytokines. Tumor necrosis factor-alpha (TNF, cachectin) is a monocyte- or macrophage-derived cytokine that has an important role as an effector molecule in various inflammatory processes. To study the possible involvement of TNF in KD, we measured the levels of circulating TNF in 39 patients with KD at various stages of the disease by using a newly developed sensitive radioimmunoassay. The TNF levels in sera from the acute and subacute phases of the disease were significantly (p less than 0.001) higher than in sera taken in the convalescence phase or in sera from children without inflammatory disease. In all patients from whom serial samples were available, the TNF level was higher during the acute and subacute phases than during convalescence. Coronary aneurysms developed in four of the patients, and these patients were among those who had the highest levels of circulating TNF during the acute and subacute phase (51.1 +/- 13.6 pg/ml (mean +/- SD) vs 30.4 +/- 15.8 pg/ml in patients without coronary aneurysms; p less than 0.001). No differences in circulating TNF levels were observed between patients who received as treatment aspirin plus intravenous immunoglobulin and those who received aspirin alone. The results show that the levels of circulating TNF are increased in acute KD and support the hypothesis that this cytokine may be involved in the pathogenesis of the vascular injury in KD.