A Swine Model of Horse Serum-Induced Coronary Vasculitis: An Implication for Kawasaki Disease

Abstract

An attempt was made to induce immune complex vasculitis by horse serum (HS) infusions in piglets, hoping to produce experimental coronary artery lesions that mimic Kawasaki disease. A total of 21 purebred male piglets of 1.5, 2.5, and 3 mo were divided into HS (n ϭ 14) and control, normal saline (NS; n ϭ 7) groups. In seven piglets, 5 mL/kg of HS was infused, then repeated with 10 mL/kg 10 d later. In another seven piglets, 10 mL/kg of HS was infused three times at 5-d intervals. In three piglets in the control group, 5 and 10 mL/kg of NS was infused at 10-d intervals. In another four piglets of the control group, 10 mL/kg of NS was infused three times at 5-d intervals. Twodimensional echocardiographic examinations for visualization and measurement of the coronary arteries were done before and after infusions at 4-to 5-d interval. Hematology examination showed that white blood cells and platelets decreased, then increased. The animals were killed at 14 -60 d after the first infusion of HS or NS, for histopathologic and immunohistochemical studies. All HS groups developed skin rashes and echocardiographic evidence of coronary artery dilation and histopathologic changes of vasculitis. None in the NS group developed vasculitis. The main changes of the coronary vasculitis were intimal proliferation, smooth muscle cell necrosis, and vacuolization changes. Those that received three HS infusions developed more skin rashes than those that received two infusions. It is concluded that piglets may serve as an experimental model for immune complex vasculitis involving the coronary arteries with skin rashes mimicking Kawasaki disease. Kawasaki disease (KD), an acute self-limiting systemic vasculitis of unknown origin, has become a leading cause of acquired heart disease other than rheumatic heart disease in many developed countries (1-3). Coronary artery lesions (CALs) with aneurysmal dilation, thrombosis, and/or stenosis, leading to myocardial infarction and death, have been recognized as the most severe complication (4, 5). Circulating immune complexes (ICs), triggered by infectious agents, bacteria, or viral or other unknown cause, have been detected in the early phase of KD, implicating that immunopathologic mechanisms might be involved in the pathogenesis of vasculitis in KD (6 -10). Attempts to produce coronary vasculitis have been made in mice, weanling rabbits, and guinea pigs by injecting infectious agents, foreign proteins, and Lactobacillus casei cell walls (11-15). Coronary arteritis was induced in weanling rabbits by injecting horse serum (HS) (16). Swine is a unique and promising animal for biomedical research, especially in the field of cardiovascular diseases (17, 18). IC coronary vasculitis, however, was never produced in swine. We tried, therefore, to induce coronary vasculitis in piglets, hoping that CAL mimicking KD could be produced. This study was designed to observe the skin and systemic reactions and hematologic changes, measure the coronary artery diameters by echocardiography, and examine the histop...

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