Phenotype and functions of natural killer cells in septic patients and its clinical significance / 中华危重病急救医学

ABSTRACT

Objective To investigate the possible mechanism of natural killer cells(NK cells)in immune dysfunction in sepsis by monitoring the phenotype and function of periphery NK cells in patients with sepsis. Methods A retrospective study was conducted. The patients with systemic inflammatory response syndrome(SIRS,n=59)or sepsis(n=65)admitted to Department of Critical Care Medicine of Anhui Provincial Hospital from August 2011 to August 2013 were enrolled. Blood samples were collected within 48 hours after intensive care unit(ICU)admission,the phenotype and function of periphery NK cells were determined by flow cytometry. Twenty-eight healthy people served as controls. Results The proportion and number of peripheral blood CD3-CD56+NK cells in SIRS and sepsis groups were normal,and no statistical difference was found when compared with those of the healthy control group〔cell proportion0.102±0.019,0.102±0.108 vs. 0.106±0.018,F=0.018,P=0.982;cell number(×106/L)182.46±65.98, 172.97±63.51 vs. 179.25±60.44,F=0.349,P=0.706〕. It was shown by NK cell degranulation detection that there was no significant difference in the expression of CD107 and interferon-γ(IFN-γ)secretion〔CD1070.135±0.050,0.140±0.058,0.128±0.070,F=0.583,P=0.560;IFN-γ(kU/L)14.36±4.74,12.49±4.21, 13.45±5.04,F=1.616,P=0.202〕among healthy control group,SIRS group,and sepsis group. It was shown by antibody dependent cytotoxic effect(ADCC)test that there was no difference in the expression of CD107 among healthy control group,SIRS group,and sepsis group(0.574±0.166,0.643±0.165,0.581±0.157,F=0.808,P=0.448). When compared with healthy controls,the secretion of IFN-γwas increased in SIRS patients(kU/L40.5±13.2 vs. 28.4±9.6,P=0.001),while reduced in sepsis patients(kU/L19.8±6.7 vs. 28.4±9.6,P<0.01). Compared with SIRS group,only NK cell surface inhibitory receptors CD158e(KIR 3DL1)expression in sepsis group was significantly increased(0.203±0.057 vs. 0.079±0.021,t=15.762,P<0.001),and there were no significant differences in the other phenotype between the two groups. Compared with SIRS group,the IFN-γproduction of the sepsis group was significantly lowered(kU/L0.280±0.040 vs. 0.310±0.038,t=3.390,P=0.009),and the level of IL-12 was also significantly decreased(ng/L0.15±0.03 vs. 0.30±0.08,t=32.832,P<0.001). Conclusion It was showed by NK cell phenotype and function assay that the function of NK cells in patients with sepsis was impaired and led to a poor production of IFN-γ. The IFN-γmediated immune dysfunction may be a main reason for the disorder of NK cell function,which laid the foundation of the clinical immune intervention practice to improve to NK cell function.