Kinetics of the Levels of Pro- and Anti-Inflammatory Cytokines and Vascular Endothelial Growth Factor in Serum and Pleural Fluid after Major Lung Resection for Lung Cancer

Some proand anti-inflammatory cytokines and angiogenesis-related factors play important roles in the inflammatory response after surgery. To study their kinetics and mutual relationships after major lung resection for lung cancer, concentrations of interleukin (IL)-6, -8 and -10 and vascular endothelial growth factor (VEGF) were measured in serum and pleural fluid. Venous blood and pleural fluid samples were collected before and up until 5 days after surgery from 10 patients with lung cancer, treated by standard lobectomy at Tottori University Hospital between 1997 and 1999. Cytokine levels after surgery were significantly higher than control levels before surgery in serum and pleural fluid. In pleural fluid, cytokines and VEGF increased after surgery 10 to 100 times than in serum. IL-6 and -10 reached their peaks in pleural fluid later than in serum, and then gradually decreased. Serum IL-8 reached its peak at 3 h, decreased until day 2 and then remained stable. Serum VEGF decreased until 3 h, and then showed little change. Pleural fluid IL-8 and VEGF reached their peaks at 3 or 6 h, decreased until day 2 and then increased up to day 5. The amount of cytokines produced per hour in drainage pleural fluid showed nearly the same kinetics as serum cytokines. Serum cytokines and VEGF showed higher coefficient values to the hourly production in pleural fluid than to the pleural fluid levels. During wound healing, IL-8 acted as a pro-inflammatory cytokine in the early phase, but as an angiogenic factor like VEGF in the late proliferative phase. The cytokine production per hour in pleural fluid is believed to be a useful marker of cytokine levels for evaluating surgical trauma after major lung resection for lung cancer.