抗肿瘤坏死因子α多克隆抗体对滑石粉和多西环素胸膜固定术效果的影响

The effects of intrapleural anti TNFα antibody on chemical pleurodesis induced by talc slurry or doxycycline

目的 研究胸膜腔内注入抗肿瘤坏死因子α(TNFα)多克隆抗体是否能够阻断滑石粉或多西环素引起的胸膜粘连。方法 34只新西兰白兔分成 2组 ,18只经胸腔插管注入 40 0mg/kg滑石粉 ;16只注入 10mg/kg多西环素。每组半数动物分别在滑石粉或多西环素注入前及注入后 12h经胸腔导管输入抗TNFα多克隆抗体 2 0 0 0U ,另半数注入同体积生理盐水对照。每 12h经胸腔导管抽尽胸液 ,直到第 4天拔管为止。术后第 2 8天处死动物 ,比较各组胸膜粘连程度。结果 滑石粉和多西环素均产生渗出液。注射多西环素组胸积液量、乳酸脱氢酶 (LDH)水平明显高于滑石粉组 ,积液白细胞数则低于滑石粉组。抗TNFα抗体对两组的胸积液量及白细胞数无明显影响。然而 ,在滑石粉组 ,注入抗TNFα抗体其胸膜粘连积分 (1 8± 0 9)明显低于未注入抗TNFα抗体组 (3 2± 0 8)。在多西环素组 ,注入抗TNFα抗体的胸膜粘连积分 (3 5± 0 5 )与未注入抗TNFα抗体积分 (3 4± 0 7)几乎一致。结论 胸腔内注入抗TNFα多克隆抗体能减少由滑石粉引起的胸膜粘连 ,但不能减少多西环素引起的胸膜粘连 。

Objective To determine whether the intrapleural injection of TNFα neutralizing Fab antibody fragment (anti TNFα Fab) would prevent the pleurodesis that occurs after the intrapleural injection of talc or doxycycline. Methods In a randomized blinded placebo controlled study, 34 New Zealand white rabbits were given 400 mg/kg talc or 10 mg/kg doxycycline intrapleurally as a sclerosant via a chest tube Half of the rabbits in each group were also given polyclonal affinity purified anti TNFα Fab 2 000 units or saline as placebo immediately before and 12 hours after the injection of the sclerosants Chest tube were aspirated at 12 hours intervals until their removal at 4 days Rabbits were sacrificed at 28 days The pleural fluid volume, cell counts, LDH and pleurodesis scores were compared among groups. Results Both talc and doxycycline produced an exudative pleural effusion The pleural fluid volume and LDH levels were significantly greater in the doxycycline group than talc group However, the pleural fluid leukocyte counts in talc group were higher than doxycycline group The administration of anti TNFα Fab had no significant effect on pleural fluid volume, LDH or leukocyte counts in either groups However, the intrapleural administration of anti TNFα Fab results in a significant decrease in the pleurodesis score for the talc group than doxycycline group (1 8±0 9 vs 3 2±0 8) In contrast the pleurodesis score was virtually identical in the doxycycline group with (3 5±0 5) and without (3 4±0 7) anti TNFα Fab. Conclusion The intrapleural administration of anti TNFα Fab diminishes the pleurodesis induced by talc but not that which results from doxycycline These findings suggest that different mechanisms are involed with the two different sclerosants