Hong-Min Luo1, Sen Hu2, Guo-yong Zhou3, Hui-Ying Bai4, Yi Lv5, Hai-Bin Wang6, Hong-Yuan Lin7, Zhi-Yong Sheng8. 1. Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: Angler200226@sohu.com. 2. Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: hs82080@yahoo.com.cn. 3. Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: bravochow@163.com. 4. Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: bhy_2152157@163.com. 5. Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: Luyi54@yahoo.com.cn. 6. Department of Clinical Laboratory, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: haibin304@hotmail.com. 7. Department of Critical Care Medicine, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: hylin@ht.ral.cn.net. 8. Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China. Electronic address: shengzhy@cae.cn.
Abstract
BACKGROUND: The aim of this study was to examine whether administration of ulinastatin inhibits pro-inflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability-evoking mediators. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), myeloperoxidase (MPO), microvascular permeability, and water content of organ tissues were evaluated in a rodent model of a 55% TBSA full-thickness scald injury. Microvascular permeability was also evaluated with a cultured pulmonary microvascular endothelial cells (PMECs) monolayer after stimulation with trypsin, bradykinin, histamine, prostaglandin E2 and burn serum. RESULTS: We found that the plasma levels of TNF-α, CRP, MPO, vascular permeability and water content of heart, lung, kidney, and small intestine tissues were significantly increased in animals after scald injury, and administration of ulinastatin lowered the levels TNF-α, CRP, MPO, vascular permeability and water content of those organ tissues. In vitro, ulinastatin lowered the levels of TNF-α, interleukin-6 (IL-6) and attenuated permeability in PMEC monolayers after being stimulated with burn serum or trypsin, but not by bradykinin, histamine or prostaglandin E2. CONCLUSIONS: These results indicate that ulinastatin attenuates the systemic inflammatory response and visceral vasopermeability both in vivo and vitro, and may serve as a therapeutic agent for prevention of systemic inflammatory response and leakage of fluid into tissue after major burn.
BACKGROUND: The aim of this study was to examine whether administration of ulinastatin inhibits pro-inflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability-evoking mediators. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), myeloperoxidase (MPO), microvascular permeability, and water content of organ tissues were evaluated in a rodent model of a 55% TBSA full-thickness scald injury. Microvascular permeability was also evaluated with a cultured pulmonary microvascular endothelial cells (PMECs) monolayer after stimulation with trypsin, bradykinin, histamine, prostaglandin E2 and burn serum. RESULTS: We found that the plasma levels of TNF-α, CRP, MPO, vascular permeability and water content of heart, lung, kidney, and small intestine tissues were significantly increased in animals after scald injury, and administration of ulinastatin lowered the levels TNF-α, CRP, MPO, vascular permeability and water content of those organ tissues. In vitro, ulinastatin lowered the levels of TNF-α, interleukin-6 (IL-6) and attenuated permeability in PMEC monolayers after being stimulated with burn serum or trypsin, but not by bradykinin, histamine or prostaglandin E2. CONCLUSIONS: These results indicate that ulinastatin attenuates the systemic inflammatory response and visceral vasopermeability both in vivo and vitro, and may serve as a therapeutic agent for prevention of systemic inflammatory response and leakage of fluid into tissue after major burn.