Triptolide as an Alternative to IVIG Therapy for Kawasaki Disease in a Mouse Model

Abstract

Background: Kawasaki disease is treated by immunoglobulin therapy, which has adverse side effects like renal damage.

Aims: The aim of the present study was to explore the effectiveness of triptolide, a compound derived from threewingnut that has anti-inflammatory effects, on the treatment of Kawasaki disease in a mouse model.

Study design: Animal experiment.

Methods: A mouse model of Kawasaki disease was established through exposure to Candida albicans by intraperitoneal injection. Exposed mice were then randomly divided into several groups (each n=15): model group (saline-treated), low- or high-dose triptolide groups (0.2 mg/kg or 0.4 mg/kg, respectively), and IVIG (high-dose immunoglobulin) group (1 g/kg body weight). Unexposed mice served as an additional control group. Nine weeks from the initial exposure, mice were euthanised and coronary tissues and blood samples were harvested. The rate of apoptosis was detected by TUNEL, and ICAM-1 expression was detected by immunohistochemistry in coronary endothelial cells. Serum TNF-α levels were detected by ELISA.

Results: Compared to mice in the (unexposed) control group, apoptosis of endothelial cells, ICAM-1 expression, and serum TNF-α levels were significantly increased in all exposed mice (p<0.05), confirming the presence of disease. However, treatment with triptolide or IVIG significantly lowered these measures compared to untreated exposed mice (model group; p<0.05).

Conclusions: Triptolide treatment reduces markers of coronary endothelial inflammation in a mouse model of Kawasaki disease, similar to IVIG treatment, and therefore may be a useful alternative therapy for this disease.

Keywords: ICAM-1; Kawasaki disease; TNF-α; Triptolide; apoptosis; endothelial cells.