Urinary trypsin inhibitor reduces inflammatory response in kidney induced by lipopolysaccharide.
Human 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 septic shock and pancreatitis. Lipopolysaccharide (LPS) triggers the sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), which potently stimulate the activation of neutrophils. The inhibitory mechanism of UTI on the systemic inflammatory response induced by the intraperitoneal injection of LPS in the kidney is unclear. This study was undertaken to examine the inhibitory effects of UTI on renal injury associated with the systemic inflammatory response induced by LPS stimulation, with emphasis on systemic TNFalpha and the activation of neutrophils in rat kidney. The systemic inflammatory response syndrome was induced by LPS treatment. Serum and renal TNFalpha, renal cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase (MPO) levels, as well as renal function after LPS stimulation, were evaluated. UTI (50,000 U/kg) inhibited LPS-induced increases in the serum and renal tissue levels of TNFalpha, as well as the renal tissue levels of CINC-1 and MPO after LPS stimulation. UTI (50,000 U/kg) also inhibited the production of serum TNFalpha associated with the systemic inflammatory response syndrome induced by LPS stimulation, thereby attenuating neutrophil infiltration into renal tissues and subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of UTI. UTI may prove useful in protecting against acute renal injury associated with a systemic inflammatory response.
Ueki
Masaaki
M
Department of Anesthesiology & Emergency Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. mueki@med.kagawa-u.ac.jp
Taie
Satoshi
S
Chujo
Kousuke
K
Asaga
Takehiko
T
Iwanaga
Yasuyuki
Y
Ono
Junichiro
J
Maekawa
Nobuhiro
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology*; D008070:Lipopolysaccharides; D008297:Male; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006023:Glycoproteins; D008070:Lipopolysaccharides; C028665:urinastatin