Suppression of coronary vasculitis in a murine model of Kawasaki disease using an angiogenesis inhibitor

Coronary arteritis can be induced in C57BL/6 mice with a single intraperito neal tip) injection of Lactobacillus casei cell fragments. Histologic secti ons resemble the vasculitis and aneurysms observed in the medium-sized coro nary arteries of children with Kawasaki disease. Since endothelial cells co uld play an important role in the development of vasculitis, a recently des cribed angiogenesis inhibitor that is not an immunosuppressive agent, AGM-1 470 (derived from Aspergillus fumigatus), was used to evaluate its therapeu tic potential in this model. A total of 32 mice were administered 0.5 mg of sterile L. casei preparation ip on day 0 and randomized to either a treatm ent (AGM-1470, 27 mg/kg sc alternate days) or a control (vehicle only) prot ocol. Hearts were harvested on day 14 (early disease) or at the end of the study on day 28 (established disease). Histologic sections were scored blin dly for vasculitis. Day 14 sections from both protocols manifested only min imal disease, indicating that the vasculitis had not yet matured. By day 28 , the AGM-1470 group had significantly less coronary vasculitis than the co ntrol group (0.7 vs 2.6, p < 0.005, respectively). These studies suggest th at endothelial cells may play an active role in this pathologic process and that angiogenesis inhibitors, such as AGM-1470, could be useful tools for the treatment and understanding of vasculitis. (C) 1999 Academic Press.