Triptolide as an alternative to IVIG therapy for Kawasaki disease in a mouse model
Triptolide as an alternative to IVIG therapy for Kawasaki disease in a mouse model
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 ef- fects, 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, re- spectively), 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 signifi- cantly increased in all exposed mice (p
___
- 1. Kim DS. Kawasaki disease. Yonsei Med J 2006;46:759-72. [CrossRef]
- 2. Burns JC. The riddle of Kawasaki disease. N Engl J Med 2007;56:659-61. [CrossRef]
- 3. Hui-Yuen JS, Duong TT, Yeung RS. TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease with coronary aneurysm in infant. J Immunol 2006;176:6294-301.
- 4. Satou GM, Giamelli J, Gewitz MH. Kawasaki disease: diagnosis, management, and long-term implications. Cardiol Rev 2007;15:163-9. [CrossRef]
- 5. Grunebaum E, Blank M, Cohen S, Afek A, Kopolovic J, Meroni PL, et al.The role of anti-endothelial cell antibodies in Kawasaki disease: in-vitro and in-vivo studies. Clin Exp Immunol 2002;130:233-40. [CrossRef]
- 6. Leung DY, Cotran RS, Kurt-Jones E, Burns JC, Newburger JW, Pober JS. Endothelial activation in the pathogenesis of Kawasaki disease. Trans Assoc Am Physicians 1989;102:131-8.
- 7. Furukawa S, Matsubara T, Jujoh K, Yone K, Sugawara T, Sasai K, et al. Peripheral blood monocyte/macrophages and serum tumor necrosis factor in Kawasaki disease. Clin Immunol Immunopathol 1988;48:247-51. [CrossRef]
- 8. Lafferty TE, DeHoratius RJ, Smith JB. Aseptic meningitis as a side effect of intravenous immune gammaglobulin. J Rheumatol 1997;24:2491-2.
- 9. Levy JB, Pusey CD. Nephrotoxicity of intravenous immunoglobulin. QJM 2000;93:751-5. [CrossRef]
- 10. Gupta N, Ahmed I, Nissel-Horowitz S, Patel D, Mehrotra B. Intravenous gammaglobulin-associated acute renal failure. Am J Hemato 2001;66:151-2. [CrossRef]
- 11. Liu MX, Dong J, Yang YJ, Yang XL, Xu HB. Progress in research on triptolide. Zhongguo Zhong Yao Za Zhi 2005;30:170-4.
- 12. Lin KX, Wang CZ, Qian GS. Effects of triptolide on apoptosis of CD4+ and CD8 + T cells. Immunological J 2000;16:24-6.
- 13. Wang HL, Yang YJ, He W, Tang DZ, Wang SJ. Effect of triptolide on cytotoxicity and NO production of activated mouse peritoneal macrophage. Zhonghua Yi Xue Za Zhi 2003;27:237-8.
- 14. Nagi-Miura N, Harada T, Shinohara H, Kurihara K, Adachi Y, Ishida-Okawara A, et al. Lethal and severe coronary arteritis in DBA/2 mice induced by fungal pathogen, CAWS, Candida albicans water-soluble fraction. Atherosclerosis 2006;186:310-20. [CrossRef]
- 15. Shinohara H, Nagi-Miura N, Ishibashi K, Adachi Y, Ishida-Okawara A, Oharaseki T, et al. Beta-mannosyl linkages negatively regulate anaphylaxis and vasculitis in mice, induced by CAWS, fungal PAMPS composed of mannoprotein-beta-glucan complex secreted by Candida albicans. Biol Pharm Bull 2006;29:1854-61. [CrossRef]
- 16. Tsujimoto H, Takeshita S, Nakatani K, Kawamura Y, Tokutomi T, Sekine I. Delayed apoptosis of circulating neutrophils in Kawasaki disease. Clin Exp Immunol 2001;126:355-64. [CrossRef]
- 17. Prasad NK, Papoff G, Zeuner A, Bonnin E, Kazatchkine MD, Ruberti G, et al. Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in human lymphocytes and monocytes: a novel mechanism of action of IVlg involving the Fas apoptotic pathway. J Immunol 1998;161:3781-90.
- 18. Leuenroth SJ, Bencivenga N, Chahboune H, Hyder F, Crews CM. Triptolide reduces cyst formation in a neonatal to adult transition Pkd1 model of ADPKD. Nephrol Dial Transplant 2010;25:2187- 94. [CrossRef]
- 19. Leuenroth SJ, Bencivenga N, Igarashi P, Somlo S,Crews CM. Triptolide reduces cystogenesis in a model of ADPKD. J Am Soc Nephrol 2008;19:1659-62. [CrossRef]
- 20. Leuenroth SJ, Okuhara D, Shotwell JD, Markowitz GS, Yu Z, Somlo S, et al. Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease. Proc Natl Acad Sci USA 2007;104:4389-94. [CrossRef]
- 21. Corson TW, Cavga H, Aberle N, Crews CM. Triptolide directly inhibits dCTP pyrophosphatase. Chembiochem 2011;12:1767-73. [CrossRef]
- 22. Leuenroth SJ, Crews CM. Triptolide-induced transcriptional arrest is associated with changes in nuclear substructure. Cancer Res 2008;68:5257-66. [CrossRef]