TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease.

Abstract

Kawasaki disease is the most common cause of multisystem vasculitis in childhood. The resultant coronary artery lesions make Kawasaki disease the leading cause of acquired heart disease in children in the developed world. TNF-alpha is a pleiotropic inflammatory cytokine elevated during the acute phase of Kawasaki disease. In this study, we report rapid production of TNF-alpha in the peripheral immune system after disease induction in a murine model of Kawasaki disease. This immune response becomes site directed, with migration to the coronary arteries dependent on TNF-alpha-mediated events. Production of TNF-alpha in the heart is coincident with the presence of inflammatory infiltrate at the coronary arteries, which persists during development of aneurysms. More importantly, inflammation and elastin breakdown in the coronary vessels are completely eliminated in the absence of TNF-alpha effector functions. Mice treated with the TNF-alpha-blocking agent etanercept, as well as TNFRI knockout mice, are resistant to development of both coronary arteritis and coronary aneurysm formation. Taken together, TNF-alpha is necessary for the development of coronary artery lesions in an animal model of Kawasaki disease. These findings have important implications for potential new therapeutic interventions in children with Kawasaki disease.

• Authors: Joyce S Hui-Yuen, Trang T Duong, Rae S M Yeung
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 10 Pg. 6294-301 (May 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16670341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor Decoy Receptors
• Tumor Necrosis Factor-alpha
• recombinant human tumor necrosis factor-binding protein-1

Topics

• Animals
• Arteritis (immunology, metabolism, pathology)
• Cell Wall (immunology)
• Coronary Aneurysm (immunology, metabolism)
• Coronary Vessels (immunology, metabolism, pathology)
• Disease Models, Animal
• Lacticaseibacillus casei (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mucocutaneous Lymph Node Syndrome (immunology, metabolism, pathology)
• Receptors, Tumor Necrosis Factor (deficiency, genetics)
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor Decoy Receptors
• Tumor Necrosis Factor-alpha (biosynthesis, physiology)