Background/Purpose: Kawasaki disease (KD) is an acute, febrile illness of childhood with sequelae of coronary artery aneurysms and cardiac fibrosis, and is the most common cause of acquired heart disease among children in the developed world. Acutely, a subset of patients with KD will demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass presumed to be due to myocardial edema and inflammation. Further, some patients will develop profound cardiac dysfunction known as Kawasaki Shock Syndrome. Here, we investigated whether inhibition of interleukin-1 activity via anakinra would correct development of the myocardial mechanical dysfunction and myocardial inflammation seen in KD.

Methods: KD was induced via the established model of lactobacillus casei cell wall extract (LCWE) injection in 4-6 week old male mice. For echocardiography and MRI, groups of mice either injected with LCWE alone, LCWE and anakinra, or normal controls were compared. Myocardial inflammation was scored by a blinded pathologist.

Results: Both imaging modalities demonstrated normalized left ventricular function in anakinra treated KD mice via measurements of ejection fraction, fractional shortening (echo) and end diastolic and systolic volumes (MRI). These were significantly (p<0.05) normalized as compared to untreated diseased KD mice. Additionally, while KD mice demonstrated increased left ventricular mass index, this was markedly attenuated (p<0.01) in anakinra treated mice. Myocardial inflammation scores were significantly (p<0.05) lower in anakinra treated vs. untreated mice.

Conclusion: Anti-interleukin-1 therapy in the mouse model of KD prevents the development of myocardial mechanical dysfunction and left ventricular mass enlargement as well as myocardial inflammatory changes. This demonstrates functional efficacy of this therapy in the treatment of children with KD, and also raises the clinical implication of anakinra treatment in patients with severe cardiac dysfunction of Kawasaki Shock Syndrome. Additionally, the demonstration of these findings in the mouse model of KD greatly bolsters the applicability of this model for human KD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anakinra-treatment-prevents-myocardial-mechanical-dysfunction-and-inhibits-histologic-evidence-of-myocardial-inflammation-in-the-mouse-model-of-kawasaki-disease/