Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Conclusion
Although there have been reports of adverse systemic effects in humans when TL has been administered intrapleurally, there have been limited reports on the systemic effects after the intrapleural administration of this low dose of SN. One study (an abstract) injected the same concentration of SN in an attempt to induce pleurodesis in patients with malignant pleural effusions. In that clinical study, 47 patients were randomized to receive 5 g TL slurry or 20 mL 0.5% SN. In that study, TL was effective in 21 of 24 patients (87.5%), and SN was effective in 22 of 23 patients (95.6%). The only significant side effect was pain requiring therapy with analgesics. No patient receiving either drug developed ARDS.
We also observed that both agents produced an acute and intense pleural inflammation, which was more pronounced with SN. For the TL group, pleural fluid WBC count, neutrophil percentage, and LDH level increased in the first 6 h and tended to decrease with time, which is similar to what was observed in the blood. For the SN group, the cellular influx to the pleural cavity was acute and was sustained with a progressive increase in LDH level.
As observed in serum, the IL-8 level in pleural fluid increased within the first 6 h after injection only in the SN group, and the VEGF level increased with time after injection with both agents, following the pattern of pleural fluid production. These findings suggest that SN tends to produce an intense compartmentalized inflammatory response that is characterized predominantly by biochemical and cytokine local production, and that IL-8 plays an important role in the recruitment of inflammatory cells to the pleural cavity in the acute phase of pleurodesis with SN. The decreased level of IL-8 in pleural fluid with time may be due to intense proteolysis, the presence of an unknown antagonist, or the action of another predominant inflammatory mediator in the pleural cavity. Pleural VEGF levels in serum increased by twofold to 12-fold for TL, and by 10-fold to 20-fold for SN, in comparison with serum levels in the control group and in animals injected with saline solution. We speculate that VEGF may be one of mediators involved in the maintenance of the inflammatory process when the levels of pleural fluid IL-8 decrease and may influence the pleural fluid production. Doxycycline
In conclusion, both TL and SN injected intrapleurally induced an acute systemic inflammatory response of variable degree. TL induced a predominantly cellular inflammatory response in the first 6 h. SN also produced a systemic response, with predominant increases in LDH, IL-8, and VEGF production. We think that further studies are needed in experimental animals and in patients receiving these agents for pleurodesis to determine the significance of these acute systemic inflammatory effects.