Song Ning, Liu Ai-jing, Gao Xue-feng, Guo Xian-li, Guan Ji-tao, Wu Jian-ling, Zhang Rui-fang, Duan Lin, He Wen-shu
Department of Respiratory Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. Email:
Zhonghua Nei Ke Za Zhi. 2013 Oct;52(10):829-32.
To investigate the effect of selective phosphodiesterase (PDE) 4 inhibitors on nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNFα) and interleukin-8 (IL-8) secreted by peripheral blood mononuclear cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD).
PBMCs isolated from 15 healthy volunteers (group A) and 20 patients with untreated active RA-ILD (group B) were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment: blank group (B1), theophylline group (B2), selective PDE4 inhibitor rolipram group (B3), and glucocorticoid group (B4) with dexamethasone. The expression of NF-κB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA).
(1) The activity of NF-κB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A (P < 0.01). Compared with group B1, three parameters above were similar to those in group B2 (P > 0.05), while group B3 and group B4 had significant decreased levels of three parameters (P < 0.01); IL-8 level in group B4 was significantly lower than that in group B3 (P < 0.05). (2) TNFα and IL-8 levels were positively correlated with NF-κB activity in group B (r = 0.902 and 0.735, P < 0.01 respectively). (3) The reduction of TNFα and IL-8 levels were positively correlated with reduction of NF-κB activity after intervention of rolipram in group B3 (r = 0.874, P < 0.01; r = 0.561, P < 0.05 respectively).
NF-κB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDE4 inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor NF-κB in PBMC, thus inhibiting the inflammatory reaction of RA-ILD.
研究选择性磷酸二酯酶（PDE）4抑制剂对诊断为类风湿关节炎合并间质性肺病（RA-ILD）患者外周血单个核细胞（PBMC）分泌的核因子κB（NF-κB）、肿瘤坏死因子-α（TNFα）和白细胞介素-8（IL-8）的影响。
从15名健康志愿者（A组）和20例未经治疗的活动期RA-ILD患者（B组）中分离PBMC并进行体外培养。将健康受试者的PBMC作为正常对照。将RA-ILD患者的PBMC分为四组进行不同处理：空白组（B1）、茶碱组（B2）、选择性PDE4抑制剂咯利普兰组（B3）和地塞米松糖皮质激素组（B4）。通过免疫细胞化学染色测定NF-κB的表达，采用酶联免疫吸附测定（ELISA）检测培养上清液中TNFα和IL-8的水平。
（1）B1组NF-κB活性以及TNFα和IL-8水平显著高于A组（P<0.01）。与B1组相比，上述三个参数在B2组与之相似（P>0.05），而B3组和B4组三个参数水平显著降低（P<0.01）；B4组IL-8水平显著低于B3组（P<0.05）。（2）B组中TNFα和IL-8水平与NF-κB活性呈正相关（r分别为0.902和0.735，P均<0.01）。（3）B3组经咯利普兰干预后，TNFα和IL-8水平的降低与NF-κB活性的降低呈正相关（r分别为0.874，P<0.01；r为0.561，P<0.05）。
NF-κB激活和促炎细胞因子参与RA-ILD的发病机制。选择性PDE4抑制剂可能通过抑制PBMC中转录因子NF-κB的活性来抑制炎性细胞因子的产生，从而抑制RA-ILD的炎症反应。
