TNF and IL-1 play essential but temporally distinct roles in driving cardiac inflammation in a murine model of Kawasaki Disease
- Author(s)
- Stock, AT; Jama, HA; Hansen, JA; Wicks, IP;
- Journal Title
- Journal of Immunology
- Publication Type
- Journal Article in press
- Abstract
- Kawasaki disease (KD) is a leading cause of pediatric heart disease, characterized by the emergence of life-threatening coronary vasculitis. Identifying which cytokines drive KD has been a major research goal, and both TNF and IL-1 have been identified as potential candidates. Using a murine model of KD induced by the injection of the water-soluble component of Candida albicans, we therefore undertook a mechanistic study to determine how and when these two cytokines mediate cardiac inflammation. In this study, we show that TNF signaling is active in the acute phase of cardiac inflammation, which is characterized by a diffuse myocarditis that precedes the development of coronary vasculitis. Mechanistically, TNF is produced by the myeloid cells and triggers acute cardiac inflammation by stimulating both stromal and immune compartments of the heart. In contrast to this early involvement for TNF, IL-1 signaling is dispensable for the development of acute myocarditis. Critically, although mice deficient in IL-1 signaling have extensive acute inflammation following C. albicans water-soluble complex challenge, they do not develop coronary vasculitis. Thus, TNF and IL-1 appear to play temporally distinct roles in KD, with TNF being active in acute cardiac inflammation and IL-1 in the subsequent development of coronary vasculitis. These observations have important implications for understanding the progression of cardiac pathology in KD and the relative therapeutic use of targeting these cytokines.
- Publisher
- AAI
- Research Division(s)
- Inflammation
- PubMed ID
- 30996002
- Publisher's Version
- https://doi.org/10.4049/jimmunol.1801593
- NHMRC Grants
- NHMRC/1023407,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-04-26 10:14:46
Last Modified: 2019-04-26 02:09:52