己酮可可碱对外源性过敏性肺泡炎治疗作用的初步研究  

Preliminary study on effect of pentoxifylline in treatment of extrinsic allergic alveolitis

作　　者：童朝辉[1] 陈宝敏 代华平[1] 王辰[1] Josune Guzman Ulrich Costabel 

机构地区：[1]首都医科大学附属北京朝阳医院北京呼吸疾病研究所,100020 [2]Ruhrlandklinik,University of Essen,essengermany45239

出　　处：《中华医学杂志》2004年第6期482-485,共4页National Medical Journal of China

基　　金：首都医学发展科研基金资助项目 (首都ZD 199901)

摘　　要：目的　通过研究己酮可可碱 (POF)对外源性过敏性肺泡炎 (EAA)患者肺泡巨噬细胞(AM)产生的细胞因子的作用 ,探讨其治疗EAA的可能性 ,并与地塞米松 (DEX)的作用进行比较。方法　入选EAA患者 9例 ,通过支气管肺泡灌洗收AM ,并以 10 %RPMI为培养液或 10 %RPMI加内毒素 (LPS ,10 0 μg/L) ;或分别加入浓度为 0 0 1mmol/L、0 1mmol/L、1mmol/L的POF ;或加入 0 1mmol/LDEX进行AM培养 2 4h。用ELISA方法测定培养上清液中细胞因子含量。结果　POF可抑制EAA患者AM自发释放的TNFα和IL 10 ,此作用有剂量依赖关系 (P <0 0 0 1和P <0 0 5 )。POF对其他自发释放的细胞因子则无影响。 0 1mmol/LDEX只抑制自发释放的TNFα(P <0 0 5 )。除IL 1β和可溶性肿瘤坏死因子受体外 ,POF和 0 1mmol/LDEX均抑制LPS刺激的其他细胞因子的释放 (P <0 0 0 1或P <0 0 1或P <0 0 5 )。结论　POF对EAA的炎症有一定的抑制作用 ,然而POF治疗EAA及其他肺部疾病的临床价值 ,需要进一步的临床试验来评价。Objectives Pentoxifylline (POF) is a well established drug with haemorrheological properties. Various evidence suggests an additional therapeutic potential in regard to inflammation and immunomodulation. Extrinsic allergic alveolitis (EAA) is a granulomatous disease which is driven by T cell and alveolar macrophage (AM) derived cytokines. To investigate the effects of POF on the production of tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, IL-8, IL-10 and the soluble TNF receptors (sTNFR1 and sTNFR2) from AM in EAA, also in comparison with dexamethasone (DEX). Methods AM from 9 patients with EAA were cultured for 24 h with 10% RPMI medium alone, or with lipopolysaccharide (LPS, 100 μg/L), and with POF at concentrations of 0.01 mmol/L, 0.1 mmol/L and 1 mmol/L, or with 0.1 mmol/L DEX. Cytokines in the culture supernatants were analysed by ELISA. Results POF induced a dose dependent suppression of spontaneous TNFα and IL-10 release from AM in EAA ( P <0.001 and P <0.05). The spontaneous production of other cytokines was unaffected by POF at all tested concentrations. DEX inhibited only the spontaneous release of TNFα significantly ( P <0.05). POF and DEX also inhibited the LPS-stimulated production of all cytokines except of IL-1β and sTNFR1 ( P <0.001 or P <0.01 or P <0.05). Conclusion Our results may be the basis for clinical trials to evaluate the role of POF as an immunotherapeutic agent in the treatment of EAA.

关 键 词：己酮可可碱 外源性过敏性肺泡炎 肺泡巨噬细胞 细胞因子 炎症反应 T淋巴细胞 

分 类 号：R563.1[医药卫生—呼吸系统] R965[医药卫生—内科学]