Objective To detect the effects of glucocorticoids on the expression of toll-like receptor 4 (TLR4) on CD14+ monocytes in peripheral blood from patients with chronic obstructive pulmonary disease (COPD) and explore the relationship between inherent immunity deficiency and the pathogenesis of COPD.Methods A total of 30 hospitalized acute exacerbations of COPD (AECOPD) patients from 2012 January to March were divided them into 2 groups of mild-moderate (A,n =15) and severe-critical (B,n =15) according to pulmonary functions.The same basic treatment (anti-infection,oxygen inhalation,bronchial smooth muscle relaxing and cough relief) was administered.And glucocorticoids were added to Group B.Two weeks later,AECOPD achieved a clinical remission and it was designated as a stable COPD group.Another 30 healthy cases over the same period were selected as control group.Flow cytometry was used to measure the relative mean fluorescence intensity (rmfi) and relative positive cell percent (rpcp) of TLR4 onr CD14 positive peripheral blood monocytes.Conventional pulmonary function test (FEV1 percentage of predicted value,FEV1/FVC value) was performed.Results The value of rmfi for TLR4 of AECOPD group was 5.14 ±0.26 and rpcp (4.24 ±0.17)％ and they were similar to those of COPD group [4.46 ±0.24 and (3.49 ± 0.24) ％ respectively,all P ＞ 0.05].AECOPD and COPD groups were both significantly lower than normal control group [13.75 ±0.28 and (10.25 ±0.13)％ respectively,all P ＜0.01].The rmfi of TLR4 of Group B was 3.12 ±0.15 and rpcp (3.17 ±0.10)％.And both were significantly lower than those of Group A [5.48 ±0.23 and (5.12 ±0.20)％ respectively,all P ＜0.01].The value of rmfi for TLR4 of Group B before glucocorticoid treatment was 3.12 ±0.15 and rpcp (3.17 ±0.10)％.And both were significantly lower than those of later glucocorticoid treatment [5.24 ± 0.25 and (5.44 ± 0.19) ％ respectively,all P ＜ 0.01].Both values were significantly lower than those of normal control group [13.75 ± 0.28 and (10.25 ± 0.13) ％ respectively,all P ＜ 0.01].The expression of TLR4 on CD14 + monocytes in peripheral blood of AECOPD patients was positively correlated with FEV1 percentage of predicted value(r1 =0.824,P＜0.001) and FEV1/FVC (r2 =0.756,P＜0.001).Conclusions Innate immunodeficiency plays an important role in the pathogenesis of COPD.And the expression of TLR4 is an important indicator for disease severity.Glucocorticoids treat COPD through inhibiting airway inflammation response and enhancing defensive function of innate immune system.%目的 研究糖皮质激素对慢性阻塞性肺疾病(COPD)患者外周血Toll样受体4(TLR4)表达的影响,探讨固有免疫缺陷与COPD的关系.方法 对2012年1-3月入住呼吸科的30例COPD急性期患者(COPD急性期组)吸氧、抗感染、解痉平喘、止咳(重-极重度组加糖皮质激素)治疗；30例中轻-中度和重-极重度者各15例,经治疗2周后全部进入临床缓解期,将这时的缓解期患者作为COPD稳定期组；另将同期门诊健康体检者30例作为正常对照组.均用流式细胞仪全血免疫荧光直标法检测外周静脉血CD14+单核细胞的TLR4水平,并检测第一秒用力呼气容积(FEV1)占预计值百分比和FEV1/用力肺活量(FVC).结果 COPD急性期组和稳定期组外周血CD14+单核细胞表面TLR4相对平均荧光强度(rmfi)和相对阳性细胞百分率(rpcp)分别为5.14±0.26与4.46±0.24和(4.24±0.17)％与(3.49±0.24)％,两组比较差异无统计学意义(P＞0.05),但均低于正常对照组的13.75 ±0.28和(10.25 ±0.13)％ (P ＜0.01).COPD急性期重-极重度患者外周血CD14+单核细胞表面TLR4 rmfi和rpcp分别为3.12±0.15和(3.17±0.10)％,低于轻-中度患者5.48 ±0.23和(5.12±0.20)％(P＜0.01).重-极重度者经糖皮质激素治疗后外周血CD14+单核细胞表面TLR4rmfi和rpcp分别为5.24±0.25和(5.44±0.19)％,高于自身治疗前(P＜0.01),但仍低于正常对照组(P＜0.05).COPD急性期患者外周血CD14+单核细胞表面TLR4表达强度与FEV1占预计值百分比和FEV1/FVC比值均呈正相关(P＜0.01),相关系数分别为0.824和0.756.结论 固有免疫缺陷在COPD发病中起作用,TLR4是反映COPD急性期病情严重程度的指标,糖皮质激素可以抑制气道炎症、增强COPD患者固有免疫防御功能.
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