CHARACTERIZATION OF THE INFLAMMATION AND IMMUNE STATUS IN SEPSIS PATIENTS AND REGULATION OF THIS INFLAMMATION BY ULINASTATIN
Abstract
Objective: Our study was designed to investigate the levels of the IL-17, IL-6, and IL-10 inflammatory mediators as well as of the T regulatory (Treg) and Th17 immune-regulation cells in patients with severe sepsis, and to observe the effect of Ulinastatin treatment on these levels.
Methods: A total of 60 patients with severe sepsis hospitalized in our ICU from October 2011 to July 2012 served as the case group, and 20 healthy individuals served as the control group. The 60 patients were randomly divided into two groups: the routine group (n=30) received routine bundle treatment and the Ulinastatin group (n=30) received routine bundle treatment + Ulinastatin treatment. Patients in the Ulinastatin group received 300,000 U Ulinastatin 3 times/day in addition to routine bundle treatment. A single course of treatment lasted 3 days. IL-17, IL-6, IL-10, Treg, Th17, and HLA-DR expression were evaluated on the third day in the ICU and then every 3 days thereafter. The effect of Ulinastatin on the patients was evaluated.
Results: The percentage of both Treg and Th17 cells in the periphery was significantly higher in the entire patient cohort than that in the control group (all P<0.01), while Treg cells were more significantly enhanced than Th17 cells. The expression rate of the IL-17 and IL-6 pro-inflammatory mediators and the IL-10 anti-inflammatory mediator was significantly higher in the entire patient cohort than that in the control group (IL-17: all P<0.01). The Treg/Th17 ratio was higher in the severe sepsis group than in the control group (P<0.01). In the severe sepsis group, the immune analysis revealed that HLA-DR expression on CD14+ monocytes was decreased compared to the control group (P<0.01]. Compared with the routine group, our study indicated that Ulinastatin treatment more effectively reduced the abnormal percentage of Treg and Th17 cells (all P<0.01) and decreased the Treg/Th17 ratio (P<0.01). Additionally, Ulinastatin ameliorated the elevated immune status of sepsis patients, as HLA-DR expression on CD14+ monocytes improved (P<0.01). Compared with the routine group, Ulinastatin treatment reduced the abnormal IL-17 and IL-6 expression (all P<0.01); while Ulinastatin also decreased IL-10 expression, this difference did not reach statistical significance. Ulinastatin also lowered the 28-day mortality of sepsis patients, but this difference did not reach statistical significance (18.7% vs. 20%; P>0.05).
Conclusions: In severe sepsis patients, the expression of the IL-10 anti-inflammatory mediator, the IL-17 and IL-6 pro-inflammatory mediators, and the percentage of Treg and Th17 cells in the periphery were abnormally enhanced. Additionally, the Treg/Th17 ratio was in disequilibrium, immune paralysis was enhanced, and HLA-DR expression decreased. Ulinastatin treatment decreased IL-17 and IL-6 expression decreased the percentage of Treg and Th17 cells, inversed the Treg/Th17 ratio, ameliorated cellular immunity, and improved HLA-DR expression. Ulinastatin treatment can, therefore, improve the prognosis of patients with severe sepsis to a certain extent.
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References
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