Presence of IFN-gamma does not indicate its necessity for induction of coronary arteritis in an animal model of Kawasaki disease.

Kawasaki disease is the most common cause of vasculitis affecting children, and the leading cause of acquired heart disease in the developed world. To date, studies on the role of IFN-gamma in the pathogenesis of Kawasaki disease have focused on peripheral production of IFN-gamma, and have yielded conflicting results. Affected heart tissue is not available from children with Kawasaki disease. In this study, we use an animal model of Kawasaki disease, Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis, to examine the role of IFN-gamma in the development of coronary artery lesions. We report the presence of IFN-gamma, both at the mRNA and protein levels, in the affected vessels. Its biphasic expression, first at days 3-7 and again at days 28-42 post-LCWE injection, corresponds to the first appearance of inflammatory infiltrate in coronary arteries, and later to vascular wall disruption and aneurysm formation, respectively. Interestingly, ablation of IFN-gamma expression did not dampen the inflammatory response, and IFN-gamma-deficient lymphocytes proliferated more vigorously in response to LCWE than those of wild-type animals. Of more importance, the incidence of coronary arteritis was the same in IFN-gamma-deficient and wild-type mice. Taken together, our findings demonstrate that IFN-gamma regulates the immune response during development of coronary arteritis, but is not required for the induction of coronary artery disease.