Related Experiment Video
Updated: Mar 15, 2026
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease
Angus T Stock1, Jacinta A Hansen2, Matthew A Sleeman3
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia stock.a@wehi.edu.au wicks@wehi.edu.au.
Insights
Granulocyte/macrophage colony-stimulating factor (GM-CSF) drives cardiac inflammation in a mouse model of Kawasaki disease (KD). Blocking GM-CSF significantly reduced heart disease, identifying it as a therapeutic target for KD.
Area of Science:
- Immunology
- Cardiovascular Research
- Pediatric Disease
Background:
- Kawasaki disease (KD) is a primary cause of pediatric heart disease.
- Inflammation in KD involves neutrophils and monocytes, leading to coronary arteritis.
- The regulators of cardiac inflammation and immune cell infiltration in KD are not well understood.
Purpose of the Study:
- To investigate the role of granulocyte/macrophage colony-stimulating factor (GM-CSF) in Kawasaki disease pathogenesis.
- To identify potential therapeutic targets for KD-associated cardiac inflammation.
Main Methods:
- Utilized a mouse model of KD induced by cell wall Candida albicans water-soluble fraction (CAWS).
- Assessed GM-CSF production by cardiac fibroblasts post-CAWS challenge.
- Evaluated the effect of GM-CSF on cardiac macrophages and inflammatory mediators.
- Tested the therapeutic efficacy of GM-CSF blockade in the mouse model.
Main Results:
- GM-CSF is rapidly produced by cardiac fibroblasts following CAWS challenge.
- GM-CSF promotes cardiac inflammation by activating local macrophages to express inflammatory cytokines and chemokines.
- Therapeutic blockade of GM-CSF significantly attenuated cardiac disease in the KD mouse model.
Conclusions:
- GM-CSF plays a critical initiating role in cardiac inflammation during Kawasaki disease.
- GM-CSF represents a promising therapeutic target for intervention in Kawasaki disease.
Abstract:
Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD.
