Objective: To investigate the effect of ulinastatin (UTI) on the levels of immune regulatory cells,pro-inflammatory mediators, and the expression of human leukocyte antigen-DR (HLA-DR) in CD14⁺ monocytes.
Methods: A total of sixty patients with severe sepsis who were admitted to intensive care unit (ICU) during October 2011 to October 2012 were enrolled. The patients were randomly divided into two groups: routine treatment group (n=30, received routine bundle treatment) and UTI group (n=30, received 30 kU UTI three times per day in addition to routine bundle treatment). A course of treatment consisted of 5 days in both groups. The peripheral blood was collected, and the expression of CD4⁺CD25⁺⁻ regulatory T cell (Treg), help T cell 17 (Th17), interleukin (IL-17, IL-6, IL-10) and HLA-DR were determined before and 5 days after treatment, in order to observe the effect of UTI.
Results: There was no significant difference in all indexes before treatment between two groups. Compared with routine treatment group, UTI could reduce the abnormal expression of Treg and Th17 in patients with severe sepsis [Treg: (9.05 ± 1.27)% vs. (11.83 ± 1.30)%, Th17:(3.20 ± 0.33)% vs. (4.42 ± 0.35)%, both P<0.01], and decrease the ratio of Treg/Th17 (2.22 ± 0.28 vs. 2.82 ± 0.29, P<0.01) more effectively. UTI could also reduce the abnormal expression of IL-17, IL-6 and IL-10 compared with routine treatment group (IL-17: 98.35 ± 12.23 ng/L vs. 118.20 ± 15.97 ng/L, IL-6: 24.17 ± 6.72 ng/L vs. 29.27 ± 8.13 ng/L, IL-10: 33.17 ± 7.24 ng/L vs. 37.34 ± 8.49 ng/L, P<0.05 or P<0.01). In addition UTI could ameliorate the immune status, improve the expression of HLA-DR compared with routine treatment group [(49.34 ± 11.34)% vs. (36.44 ± 8.14)%, P<0.01]. The 28-day mortality in UTI group showed a tendency of lowering compared with routine treatment group, but the difference between two groups was not significant(18.2% vs. 20.1%, P>0.05).
Conclusions: UTI can decrease in the expression of Treg and Th17, inverse the ratio of Treg/Th17, decrease in the expression of IL-17, IL-6 and IL-10, ameliorate the immune status, and improve the expression of HLA-DR. UTI is expected to improve the prognosis of patients with severe sepsis.