Ds. Cheng et al., The effects of intrapleural polyclonal anti-tumor necrosis factor alpha (TNF alpha) Fab fragments on pleurodesis in rabbits, LUNG, 178(1), 2000, pp. 19-29
The mechanism by which various agents produce a pleurodesis is unknown. The
purpose of this project was to determine whether the pleurodesis that resu
lts 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. Hal
f the rabbits in each group were also given 2,000 units of ovine, polyclona
l affinity purified anti-TNF alpha Fab, or saline as placebo immediately af
ter and 12 h after the injection of the sclerosant. Chest tubes were aspira
ted 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 doxycycl
ine produced an exudative pleural effusion. The pleural fluid volume and th
e pleural fluid LDH levels were significantly (p < 0.05) greater in the gro
up given doxycycline. The administration of anti-TNF alpha Fab had no signi
ficant effect on pleural fluid volume or leukocyte count in either group. H
owever, 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 pleurode
sis 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 doxy
cycline. These findings suggest that different mechanisms are involved with
the two different sclerosants.