The Potential Role of Cytokine-mediated Vascular Endothelial Activation in the Pathogenesis of Kawasaki Disease

Kawasaki disease (KD) is an acute febrile illness of infancy and early childhood characterized by diffuse vasculitis. Although the disease is generally self-limited, up to 30% of untreated patients with KD may develop coronary artery (CA) abnormalities. The acute phase of KD is characterized by marked activation of the immune system leading to increased cytokine production by immune effector cells, the induction of activation antigens on their vascular endothelium and the generation of lytic antibodies directed against vascular endothelial cells (EC) stimulated with cytokines. Treatment with intravenous gammaglobulin (IVGG) usually rapidly reduces acute clinical symptoms and prevents CA abnormalities. Immunologically, successful IVGG treatment is associated with decreased lymphocyte activation, reduced cytokine secretion and the loss of cytokine induced expression of leukocyte adhesion molecules on vascular endothelium. The association between improvement of clinical symptoms with the reduction of cytokine secretion, and reversal of EC activation supports a role for immune mediated injury to cytokine induced EC antigens in the pathogenesis of this disorder.