摘要
目的 研究己酮可可碱 (POF)对肺结节病患者肺泡巨噬细胞 (AM)产生细胞因子的作用 ,并与地塞米松 (DEX)的作用相比较。方法 收集 1 4例活动期肺结节病患者的AM ,以 1 0 %RPMI为培养液 (含有 1 0 %热灭活胎牛血清、2mmol/LL 谷氨酰胺、2 0 0kU/L青霉素及 2 0 0mg/L链霉素 ) ;或1 0 %RPMI加内毒素 (LPS ,1 0 0 μg/L) ;或分别加入浓度为 0 0 1mmol/L、0 1mmol/L和1mmol/L的POF ;或加入 0 1mmol/LDEX进行AM培养 2 4h。用酶联免疫吸附 (ELISA)法测定培养上清液中细胞因子含量。结果 POF对结节病患者AM自发释放的肿瘤坏死因子α(TNF α)有剂量依赖性抑制作用 (P <0 0 0 1 ) ,而对其他自发释放的细胞因子无影响。 0 1mmol/LDEX抑制自发释放的TNF α、可溶性肿瘤坏死因子受体 (sTNFR 2 )、白细胞介素 (IL) 1 β和IL 1 0 (P <0 0 0 1或 <0 0 5 或 <0 0 1 )。除sTNFR 1外 ,POF亦抑制这些由LPS刺激的AM释放的细胞因子 (P <0 0 5或 <0 0 0 1 )。与POF相似 ,0 1mmol/LDEX同样抑制这些LPS刺激的细胞因子释放 (P <0 0 5或 <0 0 0 1 ) ,但对sTNFR 1和IL 1 β无影响。 结论 与DEX相比 ,POF有更宽的治疗窗。用在结节病治疗上可以减少皮质激素用量或可将其替代。
Objective Pentoxifylline (POF) has recently been shown to suppress the cytokine production from lipopolysaccharide (LPS) stimulated monocytes/alveolar macrophages (AM) Sarcoidosis is a granulomatous disease which is driven by the action of tumor necrosis factor(TNF α) and other proinflammatory cytokines It was investigated that the effects of POF on the production of TNF α, interleukin (IL) 1β, IL 6, IL 8, IL 10 and the soluble TNF α receptors (sTNFR 1 and sTNFR 2) from AM in sarcoidosis, as comparison to dexamethasone (DEX) Methods AM from 14 patients with active pulmonary sarcoidosis were cultured for 24 h with RPMI medium alone, or with 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 the spontaneous TNF α release from AM in sarcoidosis ( P <0 001), while the spontaneous release of other cytokines was unaffected by POF at all tested concentrations, but a trend for the inhibition of IL 10 production was found ( P =0 092) DEX 0 1 mmol/L inhibited the spontaneous release of TNF α, sTNFR 2, IL 1β and IL 10 ( P <0 001 or <0 05 or <0 01) POF also suppressed the production of these LPS stimulated cytokines except of sTNFR 1 ( P <0 05 or <0 001) Similar to POF, DEX(0 1 mmol/L) inhibited the production of these LPS stimulated cytokines ( P <0 05 or <0 001), but not of sTNFR 1 and IL 1β Conclusions Compared with DEX, POF may improve the therapy of sarcoidosis by either sparing or replacing corticosteroids However, the precise clinical value of POF in the treatment of sarcoidosis and other lung diseases needs to be determined in further clinical trials
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2003年第7期415-418,共4页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
首都医学发展科研基金资助项目(首都ZD 199901)