Cheng D S, Rogers J, Wheeler A, Parker R, Teixeira L, Light R W
Department of Medicine, Saint Thomas Hospital, Nashville, Tennessee, USA.
Lung. 2000;178(1):19-29. doi: 10.1007/s004080000003.
The mechanism by which various agents produce a pleurodesis is unknown. The purpose of this project was to determine whether the pleurodesis that results from the intrapleural administration of talc or doxycycline depends on tumor necrosis factor alpha (TNF alpha). In a randomized, blinded, placebo-controlled study, 34 New Zealand white rabbits were given 400 mg talc or 10 mg/kg doxycycline intrapleurally as a sclerosant through a chest tube. Half the rabbits in each group were also given 2,000 units of ovine, polyclonal affinity purified anti-TNF alpha Fab, or saline as placebo immediately after and 12 h after the injection of the sclerosant. Chest tubes were aspirated at 12-h intervals until their removal at 4 days. Rabbits were killed at 28 days. The pleural fluid volume, cell counts, lactate dehydrogenase (LDH) and pleurodesis scores were compared among groups. Both talc and doxycycline produced an exudative pleural effusion. The pleural fluid volume and the pleural fluid LDH levels were significantly (p < 0.05) greater in the group given doxycycline. The administration of anti-TNF alpha Fab had no significant effect on pleural fluid volume or leukocyte count in either group. However, the administration of anti-TNF alpha Fab resulted in a significant decrease (p = 0.004) in the pleurodesis score for the animals given talc (3.2 +/- 0.8 without Fab and 1.8 +/- 0.9 with Fab). In contrast, the pleurodesis score was virtually identical in the doxycycline group with (3.5 +/- 0.5) and without (3.4 +/- 0.7) Fab. The administration of anti-TNF alpha Fab diminishes the pleurodesis induced by talc but not that resulting from doxycycline. These findings suggest that different mechanisms are involved with the two different sclerosants.
各种药物产生胸膜固定术的机制尚不清楚。本项目的目的是确定经胸腔内注入滑石粉或强力霉素所导致的胸膜固定术是否依赖于肿瘤坏死因子α（TNFα）。在一项随机、双盲、安慰剂对照研究中，34只新西兰白兔通过胸管经胸腔内给予400mg滑石粉或10mg/kg强力霉素作为硬化剂。每组中的一半兔子在注射硬化剂后即刻及12小时后还给予2000单位的羊多克隆亲和纯化抗TNFαFab或生理盐水作为安慰剂。每隔12小时抽吸胸管，直至4天后拔除。28天时处死兔子。比较各组间的胸腔积液量、细胞计数、乳酸脱氢酶（LDH）及胸膜固定术评分。滑石粉和强力霉素均产生渗出性胸腔积液。给予强力霉素组的胸腔积液量和胸腔积液LDH水平显著更高（p<0.05）。给予抗TNFαFab对两组的胸腔积液量或白细胞计数均无显著影响。然而，给予抗TNFαFab使给予滑石粉的动物的胸膜固定术评分显著降低（p = 0.004）（未给予Fab时为3.2±0.8，给予Fab时为1.8±0.9）。相比之下，强力霉素组给予Fab（3.5±0.5）和未给予Fab（3.4±0.7）时的胸膜固定术评分几乎相同。给予抗TNFαFab可减轻滑石粉诱导的胸膜固定术，但不能减轻强力霉素所致的胸膜固定术。这些发现提示两种不同的硬化剂涉及不同的机制。
