Effect of ulinastatin on cytokine reaction during gastrectomy

Abstract

BackgroundInflammation plays an important role in the postoperative morbidity of organs, which is related to the activation of pro-inflammatory and anti-inflammatory cytokines. Ulinastatin (Urinary trypsin inhibitor, UTI) is a serine protease inhibitor found in human urine or serum that inhibits the activation of human leukocyte elastase. This study examined the effect of UTI on the inflammation response in patients undergoing a gastrectomy.MethodsThirty patients scheduled to undergo a gastrectomy were divided into two groups as follows: Control group (untreated, n = 15) and UTI group (100,000 units of UTI were continuously injected intravenously for 2 hours, n = 15). Arterial blood was sampled before surgery (T0), 10 minutes after its onset (T1), at its end (T2), and 1 hour after surgery (T3) to measure the level of cytokines.ResultsBoth the control and treatment groups had higher interleukin (IL)-6 levels at T2 and T3 than T0, and the level increased with time. However, the increase was smaller in the treatment group. The IL-8 levels were not activated significantly in any of the groups.ConclusionsUTI inhibits the secretion of IL-6, which is an inflammatory cytokine produced after a gastrectomy. This shows that UTI can decrease the inflammation reaction caused by surgical stress.

Urinary trypsin inhibitor attenuates the development of neuropathic pain following spinal nerve ligation

“…Activation of PAR-2 signal sensitize peripheral nociceptors and leads to a inflammatory pain. UTI is known to inhibit serine proteases, stabilize lysosomal membranes, and inhibit inflammatory cytokine production [7,18]. Thus, it was hypothesized that the inhibition of pro-inflammatory cytokine production by UTI may prevent the initiation of persistent neuropathic pain.…”

“…Pro-inflammatory mediators such as interleukin-1␤ (IL-1␤), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-␣) are known to play important roles in the progress of pain [3,4]. Inhibition of these cytokines reduces or attenuates nerve injury-induced mechanical allodynia [5][6][7].…”

The Effect of Urinary Trypsin Inhibitor Against Neuropathic Pain in Rat Models

“…Ulinastatin is a serine protease inhibitor which is extensively used clinically in patients with pancreatitis, hemorrhage, shock, or undergoing surgery because of its anti-inflammatory and cytoprotective effects [4,6-8]. Such effects include inhibition of proteases, stabilizing lysosomal membranes, and inhibition of inflammatory cytokine production such as IL-6, IL-8, or TNF-α [6,12].…”

“…It has an anti-inflammatory effect through the inhibition of inflammatory factors by suppressing polymorphonuclear leukocyte elastase, TNF-α, and IL-6 [4]. Such anti-inflammatory effect has been known to produce the protection of cells in the case of organ injury [5,6]. Recently, it has been reported that UTI has a neuroprotective effect against cerebral injury [7,8].…”

Ulinastatin and Septic Cardiac Dysfunction

“…At the same time, in order to confirm this discovery, their research team verified this effect in the septic rat model with recombinant IL-6. However, Park, J. H. et al (Park et al 2010a) found out UTI can reduce the level of stress reaction related cytokine such as IL-6 during gastrointestinal operation, also in the trauma patients with hemorrhagic shock has the similar discovery (Park et al 2010b). This function was also verified by the septic rat model (Cao et al 2010).…”