Intravenous Immunoglobulin (IVIG) Modulation of CD40L and Nitric Oxide Expression in Kawasaki Disease

• Main Authors: WANG CHIH-LU, 王志祿
• Other Authors: YANG KUENDER
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/41090286478199937351

博士 === 長庚大學 === 臨床醫學研究所 === 92 === Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. The incidence of coronary artery lesions (CAL) is high in untreated KD. At present, high dose of intravenous immunoglobulin (IVIG) with aspirin become the standard treatment in KD. However, the exact immune modulating mechanism of IVIG in KD remains obscure. The failure rate of the IVIG treatment is higher than 10%. Since evidence has demonstrated that increases of nitric oxide (NO) and CD40L were involved in acute coronary syndrome. We attempted to investigate the relationship between NO，CD40L and IVIG. We analyzed NO levels and CD40L expression before and after IVIG treatment in patients with KD and correlated the severity of KD to immune mediators. We also exposed human umbilical vein endothelial cells (HUVEC) to plasma and mononuclear leukocytes (MNC) from patients with KD before and after IVIG to explore the mechanism of IVIG treatment of KD. Results showed that patients with KD had higher levels of NO that were significantly associated with the occurrence of CAL (p<0.001). The higher NO levels significantly decreased after IVIG treatment. The CD40L expression on CD4+ T cells and platelets from KD patients was also correlated with the occurrence of CAL. Further studies demonstrated that CD40L appeared to trigger vascular endothelial cells to release NO as well as chemokines (IL8, MCP-1) and adhesion molecules (sVCAM-1), which may be implicated in the vasculitis. Possible mechanism of the IVIG treatment in KD may be related to ligation of Fc portion of IVIG to monocytes, inducing large amount of PGE2 production. The PGE2 appeared to suppress CD40L expression on T lymphocytes. In contrast, high dose aspirin partly reversed but not decreased the IVIG downregulation of CD40L. Based on these results, we proposed that CD40L blocking antibodies or PGE2 may be used to treat KD patients; and the combination of IVIG with a high dose of aspirin treatment to KD should be appropriately adjusted.