Ulinastatin for reducing coronary lesions in Kawasaki disease

Ulinastatin for reducing coronary lesions in Kawasaki disease

Ulinastatin for reducing coronary lesions in Kawasaki disease: Higher plasma levels of neutrophil elastase and markedly activated neutrophils have been associated with poor response to intravenous immunoglobulin (IVIG) and coronary artery lesions in Kawasaki disease. Ulinastatin, a urinary trypsin inhibitor has been used as a suppressor of neutrophils. A retrospective study by Kanai T et al [1] evaluated the benefits of this drug in Kawasaki disease. They could identify 369 patients who were treated with a combination of ulinastatin, intravenous immunoglobulin and aspirin. 1178 patients who were treated with IVIG and aspirin served as the control group. They found that those treated with ulinastatin had lower rates of coronary artery lesions (3% versus 7%; P=0.01).
The drug has been tried in other conditions like pancreatitis [2], multiorgan dysfunction syndrome [3], sepsis [4] and post operative cognitive dysfunction [5]. It is considered as an immunomodulator in some of this conditions. Its anti inflammatory effects are dependent on inhibition of neutrophil derived elastase, tumour necrosis factor alpha, pro-inflammatory cytokines and interleukins. It can also suppress activation of macrophages and platelets. The medications has been approved in Japan. Clinical trials are progressing across the globe. Use in Kawasaki disease at present can be considered as an off label use.

References

1. Kanai T, Ishiwata T, Kobayashi T, Sato H, Takizawa M, Kawamura Y, Tsujimoto H, Nakatani K, Ishibashi N, Nishiyama M, Hatai Y, Asano Y, Kobayashi T, Takeshita S, Nonoyama S. Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: a retrospective study. Circulation. 2011 Dec 20;124(25):2822-8.
2. Wang LZ, Luo MY, Zhang JS, Ge FG, Chen JL, Zheng CQ. Effect of ulinastatin on serum inflammatory factors in Asian patients with acute pancreatitis before and after treatment: a meta-analysis
. Int J Clin Pharmacol Ther. 2016 Nov;54(11):890-898.
3. Atal SS, Atal S. Ulinastatin – a newer potential therapeutic option for multiple organ dysfunction syndrome.
   J Basic Clin Physiol Pharmacol. 2016 Mar;27(2):91-9.
4. Feng Z, Shi Q, Fan Y, Wang Q, Yin W.  Ulinastatin and/or thymosin α1 for severe sepsis: A systematic review and meta-analysis. J Trauma Acute Care Surg. 2016 Feb;80(2):335-40.
5. Lv ZT, Huang JM, Zhang JM, Zhang JM, Guo JF, Chen AM. Effect of Ulinastatin in the Treatment of Postperative Cognitive Dysfunction: Review of Current Literature. Biomed Res Int. 2016;2016:2571080.