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Inducible Nitric Oxide Synthase Protection Against Coxsackievirus Pancreatitis¹

Carlos Zaragoza^*, Christopher J. Ocampo^*, Marta Saura^*, Clare Bao^*, Michelle Leppo^*, Anne Lafond-Walker^*, David R. Thiemann^*, Ralph Hruban and Charles J. Lowenstein^2,*

^* Division of Cardiology, Department of Medicine, and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Coxsackievirus infection causes myocarditis and pancreatitis in humans. In certain strains of mice, Coxsackievirus causes a severe pancreatitis. We explored the role of NO in the host immune response to viral pancreatitis. Coxsackievirus replicates to higher titers in mice lacking NO synthase 2 (NOS2) than in wild-type mice, with particularly high viral titers and viral RNA levels in the pancreas. Mice lacking NOS have a severe, necrotizing pancreatitis, with elevated pancreatic enzymes in the blood and necrotic acinar cells. Lack of NOS2 leads to a rapid increase in the mortality of infected mice. Thus, NOS2 is a critical component in the immune response to Coxsackievirus infection.

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