Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expressionof prostaglandin H-2 synthase-type 2 in Kawasaki disease

Kawasaki disease is an inflammatory disease of unknown cause that causes pa nvasculitis, including coronary arteritis, Polymorphonucleocytosis in the e arly stage of the illness suggests the implication of neutrophils in the pa thogenesis of the disease. In the acute phase of Kawasaki disease, mRNA exp ression of prostaglandin H-2 synthase (PHS)-2, as determined by reverse tra nscription-polymerase chain reaction, was markedly enhanced, and thromboxan e A(2) (TXA(2))-synthesizing activity was increased in polymorphonuclear le ukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-elastase inhibitor) treatment. Lipopolysaccharide-induced enh ancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastat in in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhib its arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulina statin treatment is possibly an additional therapeutic approach to Kawasaki disease.