HMG-CoA reductase inhibition reduces T-cell activation, TNFα production, and MMP-9 gene expression in a superantigen-mediated mouse model of Kawasaki disease

• Main Author: Blankier, Shawn Adam
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2009
• Subjects: Immunology; Pharmaceutical sciences
• ISBN: 9780494589168; 0494589167

Kawasaki disease (KD) is a multisystem vasculitis leading to coronary artery aneurysm formation. In a superantigen-mediated murine model of KD, the development of coronary arteritis is mediated by T-cells through the production of TNFα. TNFα localizes to the coronary arteries, where it induces the expression of MMP-9, resulting in the breakdown of elastin and the formation of aneurysms. Statins have been recently shown to have anti-inflammatory and immunomodulatory properties as a result of the inhibition of small GTPases. In our murine model of KD, atorvastatin treatment inhibits superantigen mediated T-cell proliferation and cytokine production, including IL-2 and TNFα. Additionally, statin treatment inhibits TNFα-mediated MMP-9 production by vascular smooth muscle cells, through inhibition of the MEK/ERK pathway. Thus, statins modulate each of the critical steps in the pathogenesis of KD in a disease model, suggesting that statin use could alter the outcome and prognosis of children suffering with this disease.