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肺结核患者支气管肺泡灌洗液中某些细胞因子与受体的检测及其临床意义

Detection of some cytokines and its receptors in serum and bronchoalveolar lavage fluid in patients with pulmonary tuberculosis and its clinical significance

摘要目的 研究肺结核患者支气管肺泡灌洗液(BALF)中TNF-α及受体、IL-1β及受体的特征及其临床意义,并探讨其在结核病免疫发病中的作用.方法 采用双抗体夹心ABC-ELISA法检测46例活动性肺结核患者、21例非活动性肺结核患者BALF及血清和20例健康者血清TNF-α、可溶性TNF受体(sTNF-R)Ⅰ、IL-1β、IL-1受体水平,对其中19例活动性肺结核患者抗结核治疗后的上述细胞因子水平进行随访.组间比较采用t检验.结果 活动性肺结核组BALF中TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体水平及TNF-α/sTNF-R Ⅰ比值分别为(286.2±96.3)、(2 431.5±1 124.6)、(58.6±3.2)、(162.4±17.1)pg/L和0.06±0.01,显著高于非活动性肺结核组(t值分别为3.36、3.25、2.95、2.27和3.12,均P<0.05).空洞组BALF中TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体水平及TNF-α/sTNF-R Ⅰ比值分别为(381.4±106.4)、(2 824.7±1 318.5)、(66.4±4.6)、(176.4±18.7)pg/L和0.07±0.01,均显著高于无空洞组(t值分别为3.46、2.37、3.19、2.99和3.22,均P<0.05).抗结核治疗2个月末,19例患者中有16例患者BALF中TNF-α、sTNF-RI、IL-1β、IL-1受体水平及TNF-α/sTNF-R Ⅰ比值较治疗前明显降低(t值分别为3.26、3.17、3.28、2.92和3.12,均P<0.01),且上述患者临床症状改善,痰菌阴转,胸部X线片病灶吸收、空洞缩小或闭合.结论 TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体等均参与结核病免疫发病过程.肺结核患者BALF中TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体水平的检测可作为了解疾病活动性、判断病情及预后、监测抗结核疗效的参考.

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abstractsObjective To investigate the characteristic and its clinical value of tumor necrosis factor (TNF)-α and its receptor, interleukin (IL)-1β and its receptor in serum and bronchoalveolar lavage fluid(BALF) in patients with pulmonary tuberculosis and to determine the role of them in the immunopathogenesis of tuberculosis. Methods The concentrations of TNF-α,soluble TNF receptor (sTNF-R) Ⅰ, IL-1β and IL-1 receptor were measured using sandwish ABC-enzyme-linked immunosorbent assay (ELISA) method in serum and BALF of 46 patients with active tuberculosis and 21 patients with inactive tuberculosis, and in the serum of 20 cases of healthy control. Meanwhile the above-mentioned cytokine levels in serum and BALF of 19 patients with active tuberculosis were followed up. Differences between groups were assessed for significance by t test. Results The TNF-α,sTNF-R Ⅰ, IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of active tuberculosis group were (286.2±96.3) pg/L,(2 431.5±1 124.6) pg/L,(58.6±3.2) pg/L,(162.4±17.1) pg/L and 0.06±0.01, respectively, which were all significantly higher than those with inactive tuberculosis group (t=3.36,3.25,2.95,2.27 and 3.12 respectively; P<0.05). The TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of cavernous tuberculosis group were (381.4±106.4) pg/L,(2 824.7±1 318.5) pg/L,(66.4±4.6) pg/L,(176.4±18.7) pg/L and 0.07±0.01, respectively,which were all significantly higher than those of non-cavernous tuberculosis group (t= 3.46,2.37, 3.19, 2.99 and 3.22, respectively; P<0.05). After 2-month' antituberculosis treatments, among 19 cases, the TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of 16 cases were significantly lower than those at the beginning of treatments (t= 3.26,3.17, 3.28, 2.92 and 3.12 respectively; P<0.01). Meanwhile, their clinical symptoms improved, sputum smear negative, lesions on chest X-ray resolved and the cavity shrinked or closed. Conclusions TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor are likely to be involved in the immunopathogenesis of tuberculosis. Detection of TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor levels in the serum and BALF is helpful to understand the activity of disease, determine the clinical pattern of disease,assess the prognosis of disease and monitor the therapeutic effect in patients with pulmonary tuberculosis.

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