Effects of Urinary Trypsin Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury in Rabbits

Abstract

This study was undertaken to clarify the effects of urinary trypsin inhibitor (UTI) on lipopolysaccharide (LPS)-induced acute lung injury. Rabbits were randomly assigned to one of seven groups: saline only, UTI, LPS, pre- or post-UTI-high (infusion of UTI of 25,000 U/kg followed by 25,000 U/kg over 2 h), pre- or post-UTI-low (infusion of UTI of 2,500 U/kg followed by 2,500 U/kg over 2 h). UTI was administered 30 min before (pre-groups) or 15 min after (post-groups) LPS administration. Rabbits were mechanically ventilated with 40% oxygen for 6 h. LPS decreased peripheral blood leukocyte counts and increased wet/dry weight ratio of lung, lung injury score, neutrophil infiltration in lung, and IL-8 production in systemic blood and bronchoalveolar lavage fluid (BALF). Rabbits treated by UTI were protected from LPS-induced lung injury, as determined by wet/dry weight ratio, neutrophil infiltration in lung, lung injury score, and IL-8 in BALF levels. UTI attenuated LPS-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in sepsis-related lung injury.

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

“…However, since the onset of CA is unpredictable, hypoxic preconditioning is not applicable for patients experiencing CA. UTI, a urinary trypsin inhibitor, has been shown to possess anti-inflammatory properties and attenuate LPS-induced acute lung injury (10), inhibit systemic inflammatory responses resulting from pulmonary I/R (11) and alleviate pulmonary I/R injury via the inhibition of TNF-α expression in rats (17). In addition, previous studies have demonstrated that UTI suppresses the elevation of IL-6 and IL-8 levels in patients undergoing coronary artery bypass grafting under extracorporeal circulation (18), alleviates forebrain I/R injury by inhibiting the production of superoxide radicals and intercellular adhesion molecule-1 (19) and improves oleic acid-induced acute lung injury by reducing TNF-α levels and inducing leukocyte activation (20).…”

Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice

“…One hour after an LPS challenge, activin A-containing cells and neutrophil precursors in the bone marrow were greatly reduced in number, and activin A-containing neutrophils appeared throughout the lung. Preferential translocation of neutrophils from the bone marrow to the lungs is a characteristic feature of LPS-induced inflammation and is responsible for lung damage in such models (1,3,31,33). Neutrophils previously have been implicated as a source of activin A in lung inflammation following allergen challenge in humans (14).…”

Ulinastatin and Septic Cardiac Dysfunction

“…It was also reported that UTI, as a broad-spectrum anti-inflammatory substance, may significantly down-regulate the production of IL-8 (Cao et al 2010). Bae, H. B. et al (Bae et al 2011) discovered the level of IL-8 in the UTI preconditioning sepsis rats is significantly lower than those in sepsis rats without treatment, and associated pathological section, they hold the opinion that UTI may through inhibiting IL-8 and so on mediators of inflammation in septic rats to act as a protective role in the septic process. Also there is evidence which shows that UTI can suppress the expression of IL-8 in vitro (Nakamura et al 1997) …”