期刊
ARTHRITIS AND RHEUMATISM
卷 60, 期 7, 页码 2131-2141出版社
WILEY
DOI: 10.1002/art.24660
关键词
-
类别
资金
- Canadian Institutes of Health Research [FRN 53245]
- Arthritis Society of Canada
Objective. Kawasaki disease (KD) is a multisystem vasculitis affecting children and is characterized by immune activation in the acute stage of disease. Systemic inflammation eventually subsides, although coronary arteritis persists, resulting in aneurysm formation. KD is the leading cause of acquired heart disease among children in North America. Accepted treatment guidelines include high-dose intravenous immunoglobulin (IVIG) and aspirin in the acute phase. Although this therapy is effective, the cellular and molecular mechanisms involved are not clear. The aim of this study was to examine the effect of IVIG and salicylate at each stage of disease development. Methods. Using a murine model of KD, we established and validated several in vitro techniques to reflect 3 key steps involved in disease pathogenesis, as follows: thymidine incorporation to evaluate T cell activation, enzyme-linked immunosorbent assay to measure tumor necrosis factor alpha (TNF alpha) production, and real-time polymerase chain reaction to examine TNF alpha-mediated expression of matrix metalloproteinase 9 (MMP-9). Results. At therapeutic concentrations, IVIG, but not salicylate, effectively reduced the immune response leading to TNF alpha expression. Unexpectedly, pharmaco-logic doses of salicylate were not able to inhibit TNF alpha production and in fact enhanced its production. Neither drug directly regulated MMP-9 expression but did so only indirectly via modulating TNF alpha. TNF alpha activity was a prerequisite for local expression of MMP-9 at the coronary artery. Conclusion. Therapeutic concentrations of IVIG and salicylate differentially modulate the expression of TNF alpha and its downstream effects. Further dissection of the biologic effects of aspirin in acute KD is necessary for the rational design of therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据