It has been hypothesized that this systemic dissemination of TL is more likely if TL with a smaller mean particle size is used.- TL particles have been shown to vary markedly in median particle size.” It is hypothesized that small TL particles can enter the lymphatic system in the parietal pleura and subsequently can gain access to the systemic circulation. It should be noted that in the present study, TL with a relatively high mean particle size was used. It would be interesting to compare the systemic responses to animals that receive relatively large and relatively small TL particles. A second possible mechanism for the systemic inflammatory response induced by the administration of TL intrapleurally is the transpleural transfer of TL, which then could induce inflammation in the lung. A third possible mechanism is the systemic absorption of TL contaminants such as endotoxin.
A fourth possible mechanism is the intrapleural generation of large amounts of cytokines that could be absorbed systemically to induce a systemic inflammatory response. Indeed, the observation in the present study that the pleural fluid levels of VEGF were significantly higher than the serum levels, and that there was a significant correlation between the serum and pleural fluid levels of VEGF supports this hypothesis.
One possible explanation for the delayed maximal responses after the intrapleural injection of TL could be its persistence in the pleural space. In fact, in this study TL was visible intrapleurally at autopsy as a patchy aggregation in all rabbits that had received it.
The present study also demonstrates that the intrapleural administration of SN induced systemic effects. Although the increases in serum VEGF levels were comparable after the intrapleural injection of both agents, the intrapleural injection of TL elicited a greater increase in LDH and IL-8, and a smaller increase in the blood WBC count and percentage of neutrophils.