Inhibitory Effect of Protease-Inhibitor for Production of Interleukin 8 (IL-8) and Polymorphonuclear Leukocyte Elastase (Pmne)

Abstract

We have reported inhibitory effect (inhibitory effect of BRM) of Ulinastatin (Mochida Pharmaceutical Co., Ltd., Tokyo) and Nafamostat Mesilate (FUT-175, Babyu Pharmaceutical Co., Ltd., Tokyo) being protease-inhibitors for production of TNFα, IL-1β and IL-6 in human peripheral mononucleocytes due to endotoxin-stimulation. This time,we studied inhibitory effect due to Ulinastatin and FUT-175 for production of IL-8 in human peripheral granulocytes and human vasoendothelial cells by endotoxin-stimulation. When endotoxin-stimulation was carried out after adding Ulinastatin and FUT-175 in human peripheral granulocytes and human vasoendothelial cells, production of IL-8 was almost dose-dependently inhibited. When human peripheral granulocytes were stimulated by endotoxin after addition of Ulinastatin and FUT-175, production of elastase was dose-dependently inhibited. When human peripheral granulocytes were stimulated by endotoxin after addition of anti-IL-8 antibody, production of PMNE tended to be inhibited. It was suggested that IL-8 is related to the production of PMNE. The production of IL-8 in human peripheral granulocytes and human vasoendothelial cells due to endotoxinstimulation was inhibited by Ulinastatin and FUT-175 is effective for prevention of damage of organs developing by activation of neutrocytes due to IL-8.