Role Of Leukemia Inhibitory Factor On Pancreas And Lung Injury In Rats With Severe Acute Pancreatitis

Objective: Severe acute Pancreatitis (SAP) is a severe pancreatic inflammatory disease and its mortality rate is high. On the basis of new findings of its mechanisms, exploring new therapy is necessary. Leukemia inhibitory factor (LIF) is a multifunctional cytokine belonging to interleukin-6 family cytokines. LIF participating in the induction of inflammation as a pro-inflammatory factor has been reported. But the role of LIF on pathogenesis of acute pancreatitis and acute lung injury (ALI) in SAP rats is not clear. The objective is to observe the levels of LIF on pancreas and lung tissue in rats with SAP. Simultaneously, the possibility of LIF-targeted agents in the therapy of SAP was discussed.Methods: SAP rat model was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct. Animals were divided randomly into three groups: normal control (N= 6), sham operation (N= 6), SAP (subdivided into 3, 6, 12, 24 h post-SAP, N= 24). The LIF mRNA expression in pancreas and pulmonary tissue of SAP rat models were detected by semi-quantitative RT-PCR and the LIF protein expression were detected by immunohistochemistry.Results: 1. The level of LIF mRNA expression in pancreas was increased significantly in SAP group at 3 h in comparison with that in normal control and sham operation group (grey value: 1.071±0.074vs 1.551±0.083, 1.451±0.065, both P < 0.05), and maintained at high levels up to 24 h after modeling (grey value: 0.759±0.064, 0.613±0.075, 0.533±0.092 for 6, 12, and 24 h, respectively, P<0.01). Similarly, the expression of LIF protein in pancreas was also markedly increased in SAP group 3 and 6 h after modeling as compared with that in normal and sham operation group (grey value: 222.36±2.61, 210.90±3.05vs 229.23±3.81, 228.78±3.35, all P < 0.05), and maintained at high levels at 12 and 24 h (grey value: 205.59±2.27, 199.07±2.46,P < 0.01).2. The level of LIF mRNA expression in pulmonary was increased significantly in SAP group at 3 h in comparison with that in normal control and sham operation group (grey value: 1.018±0.065vs 1.451±0.067, 1.322±0.072, both P < 0.05), and maintained at high levels up to 24 h after modeling (grey value: 0.853±0.058, 0.635±0.064, 0.582±0.089 for 6, 12, and 24 h, respectively, P < 0.01). Similarly, the expression of LIF protein in pulmonary was also markedly increased in SAP group 3 and 6 h after modeling as compared with that in normal and sham operation group (grey value: 127.36±2.76, 122.53±2.43vs 159.46±2.78, 156.35±3.12, all P < 0.05), and maintained at high levels at 12 and 24 h (grey value: 109.37±2.87, 102.42±2.27, respectively, P < 0.01).Conclusions: LIF seems to act as a pro-inflammatory mediator in SAP. Hence, LIF may become a promising target of SAP.