Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease

J Infect Dis. 2000 Mar;181(3):1101-9. doi: 10.1086/315332.


Kawasaki disease is an inflammatory disease of unknown cause that causes panvasculitis, including coronary arteritis. Polymorphonucleocytosis in the early stage of the illness suggests the implication of neutrophils in the pathogenesis of the disease. In the acute phase of Kawasaki disease, mRNA expression of prostaglandin H2 synthase (PHS)-2, as determined by reverse transcription-polymerase chain reaction, was markedly enhanced, and thromboxane A2 (TXA2)-synthesizing activity was increased in polymorphonuclear leukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-elastase inhibitor) treatment. Lipopolysaccharide-induced enhancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastatin in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / pharmacology
  • Child
  • Child, Preschool
  • Female
  • Glycoproteins / pharmacology*
  • Humans
  • Isoenzymes / genetics*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mucocutaneous Lymph Node Syndrome / drug therapy*
  • Mucocutaneous Lymph Node Syndrome / metabolism
  • Neutrophils / metabolism
  • Pancreatic Elastase / antagonists & inhibitors*
  • Phospholipases A / genetics
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / analysis*
  • Thromboxane B2 / biosynthesis
  • Thromboxane-A Synthase / genetics


  • Glycoproteins
  • Isoenzymes
  • Lipopolysaccharides
  • RNA, Messenger
  • Thromboxane B2
  • Prostaglandin-Endoperoxide Synthases
  • Phospholipases A
  • Pancreatic Elastase
  • Thromboxane-A Synthase
  • urinastatin
  • Aspirin