Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells.
BACKGROUND
Ulinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP.


METHODS
We established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h.


RESULTS
We showed that the tissue damage of pancreas and the mortality of the SAP rats were significantly reduced by ulinastatin. We also showed that in the SAP rats the frequencies of CD4+T cells and Tregs, as well as the expressions of TGF-β1, CTLA-4, and Foxp3 were decreased in the SAP animals while IL-1β, IL-10 and TNF-α were significantly increased. Treatment with ulinastatin up-regulated the proportion of Tregs in CD4+T cells and the expression of IL-10, Foxp3 and CTLA-4 in the SAP rats in a dose dependence fashion, while down-regulating the levels of L-1β and TNF-α, myeloperoxidase (MPO) activity.


CONCLUSIONS
Our findings suggest that ulinastatin alleviates inflammatory response and tissue damage in SAP rats by increasing the proportion of Tregs. Our study provides a new mechanism for the beneficial effect of ulinastatin in SAP rat model.
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Yu
Y
Pan
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Haizong
H
Fang
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Fengchun
F
Lu
Department of Oncology and Hematology, Kaiser Permanente Medical Center, 710 Lawrence Expressway, Santa Clara, CA 95051 USA.
Minggui
M
Pan
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Fei
F
Chen
Fuzhou, People's Republic of China.
Ping
P
Xiong
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Yi
Y
Yao
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Heguang
H
Huang
Inflammatory responses; Regulatory T cells; Severe acute pancreatitis; Ulinastatin