IL-33和sST2在恶性胸腔积液和结核性胸腔积液患者胸腔积液和外周血中的表达水平及其临床意义

目的：探讨恶性胸腔积液（MPE）和结核性胸腔积液（TPE）患者胸腔积液及相应外周血中白细胞介素33（IL-33）和可溶性ST2（sST2）表达水平，阐明其临床意义。方法：选择72例胸腔积液患者（其中MPE 42例，TPE 30例），采用酶联免疫吸附测定（ELISA）法检测胸腔积液和外周血IL-33和sST2表达水平，另选本院体检正常者38人为健康对照组。比较MPE、TPE患者和健康对照组受试者胸腔积液和血清中IL-33及sST2表达水平，分析2组患者胸腔积液和血清中IL-33和sST2表达水平的相关性。采用受试者工作特征曲线（ROC曲线）确定IL-33表达水平和sST2/IL-33比值鉴别MPE和TPE的阈值及其特异度和敏感度。结果：MPE和TPE患者血清中IL-33和sST2表达水平比较差异无统计学意义（P>0.05），但均明显高于健康对照组（P<0.01）。TPE患者胸腔积液中IL-33表达水平明显高于其相应血清水平（P<0.01），MPE患者胸腔积液中IL-33表达水平明显低于其相应血清水平（P<0.05），TPE患者胸腔积液中IL-33表达水平明显高于MPE患者（P<0.05）。MPE患者胸腔积液中sST2表达水平明显高于TPE患者（P<0.01）。MPE和TPE患者胸腔积液中IL-33水平与其相应血清中IL-33水平均呈正相关关系（r_MPE=0.9304，r_TPE=0.9907，P<0.05）；MPE患者胸腔积液中sST2水平与其相应血清中sST2水平呈正相关关系（r=0.934 5，P<0.05），但TPE患者胸腔积液中sST2水平与其相应血清中sST2水平无相关性。ROC曲线结果，鉴别TPE和MPE的胸腔积液中IL-33表达水平的最佳阈值为17.08 ng·L^-1，相应敏感度和特异度分别为96.7%和92.9%；胸腔积液中sST2/IL-33比值鉴别TPE和MPE的最佳阈值为15.06，相应敏感度和特异度分别为96.8%和95.5%。结论：IL-33和sST2不同程度地参与了TPE和MPE的胸膜炎症反应。监测胸腔积液中IL-33表达水平和sST2/IL-33比值可能是鉴别良、恶性胸腔积液的新方法，有较高的临床应用价值。

Expression levels of IL-33 of interleukin-33 and sST2 in pleural effusion and peripheral blood of patients with malignant and tuberculous pleural effusion and their clinical significances

Objective: To investigate the expression levels of interleukin-33 (IL-33) and soluble ST2(sST2) in the pleural effusion and the corresponding peripheral blood of the patients with malignant pleural effusion (MPE) and tuberculous pleural effusion(TPE),and to clarify their significances.Methods: A total of 72 patients with pleural effusion were selected (42 cases of MPE,30 cases of TPE).The expression levels of IL-33 and sST2 in the pleural effusion and peripheral blood were measured by ELISA.Another 38 healthy controls were selected as healthy control group.The expression levels of IL-33 and sST2 in the pleural effusion and peripheral blood were compared between MPE,TPE patients, and healthy people.The correlation between the expression levels of IL-33 and sST2 in the pleural effusion and serum of the patients in two groups were analyzed. The IL-33 level and the ratio of sST2/IL-33 were obtained using receiver operating characteristic curve (ROC) to identify the cut-off values of MPE and TPE and the corresponding sensitivity and specificity.Results: There was no statistical significance in the expression levels of serum IL-33 and sST2 between MPE and TPE (P>0.05),but they were higher than those in healthy control group (P<0.01).The expression level of IL-33 in pleural effusion of the TPE patients was higher than that in the corresponding serum (P<0.01),but the expression level of IL-33 in pleural effusion of the MPE patients was significantly lower than that in the corresponding serum (P<0.05).The expression level of IL-33 in pleural effusion of the TPE patients was significantly higher than that of the MPE patients(P<0.05).The expression level of sST2 in pleural effusion of the MPE patients was higher than that of the TPE patients (P<0.01). The expression levels of IL-33 in pleural effusion in MPF (r_MPF=0.930 4) and TPE(r_TPF=0.990 7) patients were positively correlated with those in corresponding serum; the expression level of sST2 in pleural effusion of the MPE patients was positively correlated with sST2 level in the corresponding serum (r=0.934 5),but there was no correlation in the TPF patients.The cut-off value of IL-33 expression level in pleural effusion for the differential diagnosis of TPE and MPE was 17.08 ng·L^-1,with the corresponding sensitivity of 96.7% and the specificity of 92.9%,respectively.The cut-off value of sST2/IL-33 ratio in pleural effusion for the differential diagnosis of TPE and MPE was 15.06,with the corresponding sensitivity of 96.8% and the specificity of 95.5%,respectively.Conclusion: IL-33 and sST2 are likely to participate in the inflammatory response of pleurisy of TPE and MPE in different degrees.The montoring of expression level of IL-33 in pleural effusion and the ratio of IL-33/sST2 may be a new method for the differential diagnosis of MPE and non-MPE with better clinical application value.