Do the effects of a protease inhibitor, ulinastatin, on elastase release by blood transfusion depend on interleukin 6?

Objective: Blood transfusion induces polymorphonuclear leukocyte elastase (PMNE) and interleukin 6 (IL-6). IL-6 would activate neutrophils to release PMNE. Ulinastatin, a protease inhibitor, inhibits PMNE release by blood transfusion. The purpose of this study was to investigate whether the effects of ulinastatin on PMNE release by blood transfusion come through inhibition of IL-6. Design: Semirandomized, controlled clinical trial. Setting., Surgical center in a university hospital. Patients., Patients age 35-70 yrs undergoing gastrectomy were enrolled in this study until the four study groups had 12 patients each. Interventions: Half of the enrolled patients received ulinastatin at random. After surgery, patients were divided into the following four groups., group A received neither blood transfusion nor ulinastatin, group B received only blood transfusion, group C received only ulinastatin, and group D received both blood transfusion and ulinastatin. The infusion of ulinastatin 300,000 units was started at manipulation of the stomach in the group C and at the start of blood transfusion in the group D. Measurements and Main Results., Segmented neutrophil count and plasma concentrations of PMNE and IL-6 were measured. In addition, PMNE and IL-6 concentrations in every unit of concentrated red blood cell transfused and these concentrations in the plasma of the recipient after every unit of transfusion were measured. Results: Blood transfusion increased plasma concentrations of PMNE and IL-6, and the PMNE release from segmented neutrophil. The increase of plasma PMNE but not IL-6 concentration after each unit of blood transfusion was inhibited by ulinastatin. However, ulinastatin did not inhibit the increase of plasma concentrations of PMNE and IL-6 by surgical stimuli of gastrectomy. Conclusions: Ulinastatin 300,000 units might be useful to inhibit blood transfusion-induced increase of PMNE but not IL-6. The inhibition of PMNE increase by ulinastatin was independent of IL-6.