Ulinastatin, an Elastase Inhibitor, Inhibits the Increased mRNA Expression of Prostaglandin H2 Synthase-Type 2 in Kawasaki Disease

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. Kawasaki disease (mucocutaneous lymph node syndrome) is a febrile disease in early childhood that is characterized by high fever for 15 days, bilateral conjunctivitis, polymorphous rash, cervical lymphadenopathy, indurative edema of hands and feet followed by desquamation of skin, and changes in lips and mouth: reddened, dry or cracked lips, strawberry tongue, and diffuse redness of oral mucosa. The most important complication is coronary arteritis leading to the formation of aneurysm. Although the cause of Kawasaki disease is entirely unknown, many investigators speculate that viral, bacterial, or both types of infections are involved in some form in the beginning of the disease. In the early stage of the illness, laboratory examinations show polymorphonucleocytosis and marked elevation of levels of C-reactive protein (CRP) [1]. These findings are often accompanied by bacterial infection. Polymorphonucleocytosis in the acute phase of the disease suggests a possible implication of neutrophils in the inflammatory process in vascular lesions. Recent studies showed that numbers of lipopolysaccharide (LPS)‐positive polymorphonuclear leukocytes (PMNL), which were measured by flow cytometry by use of anti-LPS antibody, were increased and that plasma levels