T淋巴细胞亚群及Th1/Th2细胞因子谱早期鉴别细菌尿源性脓毒症

目的探究尿源性脓毒症患者T淋巴细胞亚群及辅助性T细胞1(Th1)/Th2细胞亚群细胞因子谱水平变化及其对革兰阳性菌、革兰阴性菌的鉴别价值。方法选择2015年2月-2020年3月遵义医科大学附属医院收治的98例尿源性脓毒症患者、80例常规泌尿系统感染患者及100名查体的健康志愿者作为研究对象,分别纳入脓毒症组、局部感染组、对照组。对脓毒症组患者进行病原菌分析,检测T淋巴细胞亚群比例及白细胞介素-2(IL-2)、IL-4、IL-6、IL-10、肿瘤坏死因子(TNF-α)、干扰素-γ(IFN-γ)等细胞因子水平。结果入组脓毒症患者中,革兰阴性菌引起的尿源性脓毒症患者共53例(检出革兰阴性菌53株),以大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌为主;革兰阳性菌引起的尿源性脓毒症患者共45例(检出革兰阳性菌45株),以表皮葡萄球菌、粪肠球菌、金黄色葡萄球菌、溶血葡萄球菌为主。脓毒症组患者CD₃⁺T淋巴细胞亚群比例、CD₄⁺T淋巴细胞亚群比例、CD₄⁺/CD₈⁺分别为(59.84±7.41)%、(34.84±5.26)%、(1.42±0.65),低于局部感染组、对照组,而IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ分别为2.69(0.98,16.23)pg/ml、2.49(0.74,22.74)pg/ml、88.41(10.24,188.52)pg/ml、25.63(1.74,74.15)pg/ml、3.25(1.01,16.96)pg/ml、7.11(1.22,15.63)pg/ml,高于局部感染组、对照组(P<0.05)。革兰阳性菌感染患者CD₃⁺、CD₄⁺、CD₄⁺/CD₈⁺分别为(64.15±4.71)%、(37.41±5.41)%、(1.53±0.34),高于革兰阴性菌感染患者,IL-6、IL-10、TNF-α分别为70.12(15.26,152.37)pg/ml、10.89(2.22,35.96)pg/ml、2.88(1.01,15.27)pg/ml,低于革兰阴性菌感染患者(P<0.05)。CD₃⁺、CD₄⁺、CD₄⁺/CD₈⁺、IL-6、IL-10等指标鉴别革兰阳性菌感染及革兰阴性菌感染的曲线下面积分别为0.651、0.681、0.656、0.769、0.758,当截点值为61.70%、35.10%、1.47、77.41 pg/ml、17.16 pg/ml时约登指数最大。结论尿源性脓毒症患者存在T细胞亚群及Th1/Th2细胞因子谱水平的失衡,且革兰阳性菌及革兰阴性菌脓毒症患者存在一定差异,临床可根据这些指标进行早期诊断及病原菌类型的鉴别。

T lymphocyte subsets and Th1/Th2 cytokine profile in the early identification of bacteria in urinary sepsis

OBJECTIVE To explore the changes of T lymphocyte subsets and T helper 1(Th1)/Th2 cytokine profile in patients with urinary sepsis and their value in identifying Gram-positive bacteria(G+) and Gram-negative bacteria(G-). METHODS From Feb. 2015 and Mar. 2020, 98 patients with urinary sepsis(sepsis group) and 80 patients with routine urinary system infection(local infection group) admitted to Affiliated Hospital of Zunyi Medical University, and 100 healthy volunteers(control group) were selected as the research subjects, and were included in the toxicosis group, local infection group, and control group, respectively. Pathogenic bacteria in the sepsis group were analyzed. The proportion of T lymphocyte subsets, levels of cytokines interleukin-2(IL-2), interleukin-4(IL-4), interleukin-6(IL-6), interleukin-10(IL-10), tumor necrosis factor(TNF-α), and interferon γ(IFN-γ) were detected. RESULTS Among the included patients with sepsis, a total of 53 patients with urinary sepsis caused by gram-negative bacteria(53 Strains of gram-negative bacteria), including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, respectively, 45 patients with patients with urinary sepsis caused by gram-positive bacteria(45 strains of gram-positive bacteria), including Staphylococcus epidermidis, Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus hemolyticus, respectively. The proportion of CD₃⁺ T lymphocyte subsets, CD₄⁺ T lymphocyte subsets, and CD₄⁺/CD₈⁺ in the sepsis group were(59.84±7.41)%,(34.84±5.26)% and(1.42±0.65), respectively, lower than those in the local infection group, and those in the control group. While the levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were 2.69(0.98, 16.23) pg/ml, 2.49(0.74, 22.74) pg/ml, 88.41(10.24, 188.52) pg/ml, 25.63(1.74, 74.15) pg/ml, 3.25(1.01, 16.96) pg/ml and 7.11(1.22, 15.63) pg/ml, respectively, higher than those in the local infection group and the control group. The CD₃⁺, CD₄⁺, and CD₄⁺/CD₈⁺ in patients with G- bacterial infection were(64.15±4.71)%,(37.41±5.41)% and(1.53±0.34), respectively, higher than those of patients with G- bacterial infection. The levels of IL-6, IL-10 and TNF-α were 70.12(15.26,152.37) pg/ml, 10.89(2.22,35.96) pg/ml and 2.88(1.01, 15.27) pg/ml, respectively, significantly lower than those of patients with G- bacterial infection(P<0.05). The area under curve of CD₃⁺, CD₄⁺, CD₄⁺/CD₈⁺, IL-6, IL-10 and other indicators for distinguishing G+ bacterial infection and G- bacterial infection were 0.651, 0.681, 0.656, 0.769, and 0.758, respectively. When the cutoff values were 61.70%, 35.10%, 1.47, 77.41 pg/ml, and 17.16 pg/ml, the Youden index was the highest. CONCLUSION Patients with urinary sepsis have imbalanced T lymphocyte subsets and Th1/Th2 cytokine profile levels, and there are certain differences between G+ and G- in patients with sepsis. Clinically, early diagnosis and identification of pathogenic bacteria can be made based on these indicators.