Effect of ulinastatin on the apoptosis of regulatory T cells and cytokine secretion in septic mice

Objective To investigate the effect of ulinastatin on the apoptosis of regulatory T cells (Tregs) and cytokine secretion in septic mice. Methods A total of 60 male mice were randomized into the sham group, model group and ulinastatin group, 20 mice in each group. The model of sepsis was reproduced by cecal ligation and perforation, the mice in the sham group received celiotomy without ligation and puncture, and the mice in the ulinastatin group were given 100 000 U/kg ulinastatin by tail intravenous injection at 30 min after operation. The apoptosis rates of regulatory T cells were detected by flow cytometry, and the level of interleukin-2 (IL-2), IL-4 and interferon γ were determined by enzyme-linked immunosorbant assay. Results The apoptosis rates of Tregs in the sham group, model group and ulinastatin group showed significant differences [(20.1 ± 1.0)%, (10.9 ± 0.8)%, (13.7 ± 0.8)%, F = 10.236, P = 0.030], and the apoptosis rates of Tregs in the ulinastatin group were much lower than those in the sham group, and much higher than those in the model group (all P < 0.05). Meanwhile, the levels of IL-2 [(352 ± 76), (172 ± 59), (249 ± 64) ng/L] and interferon γ [(177 ± 25), (56 ± 14),(109 ± 18) ng/L] in the model group and ulinastatin group decreased obviously as compared with the sham group, and it decreased most in the model group (all P < 0.05). The levels of IL-4 in the model group and ulinastatin group were much higher than those in the sham group, and were highest in the model group [(46 ± 15), (328 ± 81), (242 ± 62) ng/L, all P < 0.05]. Conclusion Ulinastatin may induce the apoptosis of Tregs, improve the levels of IL-2 and interferon γ, and reduce the levels of IL-4. Key words: Sepsis; Apoptosis; Cytokines; Regulatory T cells; Ulinastatin; Mice