Candida albicans -Extract Causing Systemic Vasculitis in Mice as an Animal Model of Kawasaki Disease

Abstract

We established a systemic vasculitis mice model involving coronary arteries using C. albicans-Extract. This model is evaluated as an animal model of Kawasaki disease (KD) since this model has many similar points of KD. Careful study of this model may provide fundamental information that increases our understanding of the pathogenesis, natural history, and appropriate therapy of this illness. Yeast cells of a C. albicans strain isolated from the feces of a KD patient were incubated at 37°C for 72 hours. After harvest, the extract was obtained from the yeast cells using boiling water and KOH. C. albicans-Extract suspended in PBS was injected intraperitoneally for five consecutive days at 1st and 5th week. At 9th week, mice were killed under anesthesia, and then, histological features of the arteritis in various organs were observed. There was a difference in susceptibility to vasculitis between inbred mice strains. BALB/c, DBA/2 and CBA/J mice were resistant to vasculitis, however, C3H/HeN and C57BL/6 mice were classified as sensitive strains. Coronary arteries were most frequently involved; aorta and other medium-sized arteries in kidney, retroperitoneum, testis etc. were sometimes involved. Vasculitis was defined as a productive inflammation, which shows dense infiltrates of large mononuclear cells and polymorphonuclear cells at the adventitia and/or media of arteries with an association of a few small round cells. Fibrinoid necrosis was rarely seen. Most of mononuclear cells and polymorphonuclear cells were positive for CD11b, and small round cells were positive for CD4, CD8a or CD45RB. ICAM-1 was usually expressed on endothelial cells of arteries. IFN-γ was expressed on small round cells and large mononuclear cells, but IL-12 and IL-4 were not expressed in any cells. An expression of TNF-α and IL-6 were usually demonstrated on large mononuclear cells, small round cells and endothelial cells.