Effects of Perioperative Protease Inhibitor on Inflammatory Cytokines and Acute-Phase Proteins in Patients with Hepatic Resection

Abstract

Aim: The objective of this study was to examine the effects of perioperative administration of ulinastatin, or urinary trypsin inhibitor (UTI), on inflammatory cytokines and acute-phase proteins induced by inflammatory cytokines in patients who had undergone hepatic resection. Method: Twenty patients admitted to the hospital for hepatic resection were equally randomized to one of two groups: the UTI group, those who were administered perioperative UTI, and the control group. Results: The UTI group had no adverse effects from using UTI. Production of serum interleukin-6 (IL-6) tended to be attenuated in the UTI group when compared with the control group. Moreover, the UTI group had significantly decreased positive acute-phase C-reactive protein (p < 0.05) and significantly increased negative acute-phase protein prealbumin and retinol-binding protein (p < 0.05). Serum IL-6 levels significantly correlated with serum C-reactive protein levels on postoperative day 1 (r = 0.70, p < 0.01). Conclusion: These results suggest that perioperative administration of UTI might deserve further assessment for use in modulating acute-phase responses without adverse effects in patients who have undergone hepatic resection.

The effect of ulinastatin on hemostasis in major orthopedic surgery

“…The dose of ulinastatin and the timing of administration can also be limiting factors. To examine the perioperative effect of ulinastatin on inflammatory cytokines, ulinastatin was given at a dosage of 150,000 units every 12 hours from the start of induction of anesthesia until the fourth postoperative day [26]. Ulinastatin significantly modulated the acute phase response in the circulatory shock subsequent to hepatic resection.…”

Neutrophil Elastase Inhibitor (Sivelestat) Preserves Antitumor Immunity and Reduces the Inflammatory Mediators Associated with Major Surgery

“…It was recently found that the perioperative administration of protease inhibitor suppressed a marked increase in IL-6 and it was also useful for reducing surgical stress. 3,14,15 These reports described the clinical benefi ts of gabexate mesilate or urinary trypsin inhibitor, which were not specifi c protease inhibitors. It is known that activated neutrophils can cause tissue injury by releasing proteases.…”

Perioperation ulinastatin intervention protects liver function in hepatectomy: a systematic review of randomized controlled trials and meta-analysis

“…Ulinastatin or urinary trypsin inhibitor (UTI) is a Kunitz-type serine protease inhibitor that plays an antiinflammatory effect by inhibiting several proteases such as trypsin, plasmin, cathepsin G, chymotrypsin, and neutrophil elastase (6). Animal studies (7)(8)(9)(10) and human studies (11,12) showed that UTI administration suppressed acute inflammatory responses after hepatectomy. Since there was no systematic review or meta-analysis of randomized controlled trials (RCTs) to assess the benefits of UTI in hepatectomy, whether perioperatively UTI using has a protective effect on liver function remained unclear.…”