Protective effects of urinary trypsin inhibitor on systemic inflammatory response induced by lipopolysaccharide

Ken-Ichiro Inoue, Hirohisa Takano, Rie Yanagisawa, Toshikazu Yoshikawa, Ken-Ichiro Inoue, Hirohisa Takano, Rie Yanagisawa, Toshikazu Yoshikawa

Abstract

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used in Japan as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation (DIC), shock, and pancreatitis. Recent in vitro studies have demonstrated that serine protease inhibitors may have anti-inflammatory properties beyond their inhibition of neutrophil elastase at the site of inflammation. However, the therapeutic effects of UTI in vivo remain unclear. In this review, we introduce the roles of UTI in the experimental systemic inflammatory response induced by both intraperitoneal and intratracheal administration of lipopolysaccharide using UTI deficient and wild-type mice. Our experiments suggest that UTI can protect against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly, through the inhibition of proinflammatory cytokine and chemokine expression. UTI may therefore present an attractive "rescue" therapeutic option for systemic inflammatory response syndromes such as DIC, acute lung injury, and multiple organ dysfunction.

Keywords: cytokine; fibrinogen; lipopolysaccharide; urinary trypsin inhibitor.

Figures

Fig. 1
Fig. 1
Shematic representation of the protective role of UTI against SIRS induced by LPS in mice. Our data suggest that UTI is protective against 1) endothelial activation/damage, 2) proinflammatory cytokine and chemokine production and/or release, 3) fibrinogen synthesis, 4) neutrophil recruitment into organs, and/or 5) organ injury.

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