@article {Riffo-VasquezP2134, author = {Yanira Riffo-Vasquez and Clive Page}, title = {Anti-inflammatory activity of doxofylline and theophylline in LPS-induced lung inflammation}, volume = {40}, number = {Suppl 56}, elocation-id = {P2134}, year = {2012}, publisher = {European Respiratory Society}, abstract = {Doxofylline and theophylline are two xanthine drugs that show both bronchodilator and anti-inflammatory actions. Data has suggested that doxofylline has a wider therapeutic window than theophylline however, the precise mechanism of action of doxofylline is unknown and its anti-inflammatory activity has not been widely investigated. Methods: Doxofylline (0.3 mg/kg i.p.) and Theophylline (10 mg/kg, i.p.) were given -24, -1 and 6 h after LPS (10 {\textmu}g/mice, i.n.) in Balb/c mice. Lung lavage was performed 24 h later. In other experiments, doxofylline (0.3 mg/kg, i.p.) was given -24, -1 and 6 h after injection of LPS (10 {\textmu}g) into the scrotal sac. Mice were prepared for intravital microscopy 24h later. Results: LPS recruited significantly higher number of neutrophils (PMN) to the lung (mean{\textpm}SEM) compared to saline (saline:0{\textpm}0 vs LPS:2.4{\textpm}0.2 x106cells/ml, n =4). Doxofylline (Doxo) significantly inhibited the recruitment of PMN (LPS/Doxo:1.4{\textpm}0.2 x106cells/ml, n =4; p\<0.05 vs LPS alone). Theophylline (Theo) did not alter the recruitment of PMN in response to LPS (LPS:1.9{\textpm}0.2 x106cells/ml vs LPS/Theo:2.5{\textpm}0.2 x106cells/ml, n=8). Mice showed an accumulation of cells in the tissue (cells/50{\textmu}m2) (saline:0{\textpm}0 vs LPS:9.3{\textpm}2.5, n=4; p\<0.05) and higher number of cells rolling (cells x100{\textmu}m2) in 30 sec (saline:0.2{\textpm}0.2 vs LPS:5.3{\textpm}2.4, n =4, p\<0.05) 24 h after LPS injection into the scrotal sac. Doxofylline significantly inhibited cell migration in response to LPS (LPS/Doxo:3.1{\textpm}1.9, n=4; p\<0.05 vs LPS alone) but significantly increased cell rolling (10.2{\textpm}3.0, n=4; p\<0.05 vs LPS alone). Conclusion: Doxofylline significantly reduced cell transmigration in response to LPS, supporting an anti-inflammatory action.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/40/Suppl_56/P2134}, eprint = {https://erj.ersjournals.com/content/40/Suppl_56/P2134.full.pdf}, journal = {European Respiratory Journal} }