Abstract 70: Trial of Ulinastatin treatment for murine model of Kawasaki Desease

Abstract

Recently, we reported that the initial Ulinastatin (UTI) therapy combined with intravenous immunoglobulin (IVIG) reduced the proportion of patients with Kawasaki disease requiring additional rescue treatment and the occurrence of coronary artery lesions as compared with IVIG alone (Circulation. 2011;124(25):2822-2828.). However, there have been no reports that histologically examined the therapeutic effects of UTI., In the present study, to investigate the histological efficacy of UTI, we administered UTI in a vasculitis murine model, resembling Kawasaki disease Four-week-old male mice DBA/2 were intraperitoneally administered Candida albicans water soluble extract (CAWS) for 5 days and were treated either with UTI, IVIG, or a combination of UTI and IVIG. Further, we examined the plasma levels of neutrophil elastase andcytokinesandevaluated histopathological features.. Neutrophil elastase, TNF-α, IL-6, IP-10, and MIG significantly increased in the CAWS-treated mice. Large amount of elastase-positive neutrophils infiltrated in the coronary tissue. In addition, the infiltration of elastase-positive neutrophils was reduced in the pathological tissue of the UTI treatment group. Neutrophil elastase is strongly involved in the destruction of the elastic plate and smooth muscle layer. There is a possibility that destruction of the vascular structures can be suppressed by decreasing the elastase-positive neutrophils infiltration in the UTI treatment group.