CAJ | 학술논문

目的探讨选择性磷酸二酯酶4(PDE4)抑制剂对类风湿关节炎(RA)合并间质性肺疾病(ILD)患者外周血单个核细胞(PBMC)体外产生促炎性细胞因子的影响及机制,为选择性PDE4抑制剂治疗RA合并ILD提供理论依据.方法采集15例健康志愿者(健康对照组)和20例初治活动期RA合并ILD患者(RA合并ILD组)的PBMC.RA合并ILD组PBMC分为空白对照组、茶碱组、咯利普兰组和地塞米松组,免疫细胞化学法检测PBMC核因子-κB (NF-κB) p65阳性细胞百分率,酶联免疫吸附测定法(ELISA)检测PBMC培养上清中肿瘤坏死因子α(TNFα)、白细胞介素-8(IL-8)水平.结果 (1)健康对照组、RA合并ILD组中咯利普兰组、地塞米松组PBMC培养上清中TNFα、IL-8水平和NF-κB p65阳性细胞百分率低于空白对照组(P＜0.01),咯利普兰组、地塞米松组低于茶碱组(P＜0.01)；地塞米松组IL-8水平低于咯利普兰组(P＜0.05).(2)相关性分析:RA合并ILD组PBMC培养上清中NF-κB p65阳性细胞百分率与TNFα、IL-8水平呈正相关(r值分别为0.902、0.735,P＜0.01).咯利普兰组NF-κBp65阳性细胞百分率与TNFα、IL-8水平呈正相关(r=0.874,P＜0.01;r =0.561,P ＜0.05).结论 RA合并ILD患者PBMC NF-κB活化并产生促炎性细胞因子,参与了RA合并ILD的发病过程；选择性PDE4抑制剂可能通过抑制NF-κB活性抑制PBMC产生促炎性细胞因子,从而抑制RA合并ILD的炎症反应.
목적 탐토선택성린산이지매4(PDE4)억제제대류풍습관절염(RA)합병간질성폐질병(ILD)환자외주혈단개핵세포(PBMC)체외산생촉염성세포인자적영향급궤제,위선택성PDE4억제제치료RA합병ILD제공이론의거.방법 채집15례건강지원자(건강대조조)화20례초치활동기RA합병ILD환자(RA합병ILD조)적PBMC.RA합병ILD조PBMC분위공백대조조、다감조、각리보란조화지새미송조,면역세포화학법검측PBMC핵인자-κB (NF-κB) p65양성세포백분솔,매련면역흡부측정법(ELISA)검측PBMC배양상청중종류배사인자α(TNFα)、백세포개소-8(IL-8)수평.결과 (1)건강대조조、RA합병ILD조중각리보란조、지새미송조PBMC배양상청중TNFα、IL-8수평화NF-κB p65양성세포백분솔저우공백대조조(P＜0.01),각리보란조、지새미송조저우다감조(P＜0.01)；지새미송조IL-8수평저우각리보란조(P＜0.05).(2)상관성분석:RA합병ILD조PBMC배양상청중NF-κB p65양성세포백분솔여TNFα、IL-8수평정정상관(r치분별위0.902、0.735,P＜0.01).각리보란조NF-κBp65양성세포백분솔여TNFα、IL-8수평정정상관(r=0.874,P＜0.01;r =0.561,P ＜0.05).결론 RA합병ILD환자PBMC NF-κB활화병산생촉염성세포인자,삼여료RA합병ILD적발병과정；선택성PDE4억제제가능통과억제NF-κB활성억제PBMC산생촉염성세포인자,종이억제RA합병ILD적염증반응.
Objective 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 mononuclcar cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD).Methods 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).Results (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).Conclusion 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.