EPS1.8 The anti-inflammatory activity of the mucociliary clearance agent brevenal enhances the efficacy of cystic fibrosis therapies

Brevenal, a Marine Natural Product, is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells

“…Brevenal, a natural product isolated from marine algae, has been shown to increase mucociliary clearance in animal models of chronic respiratory disease [19]. Brevenal also demonstrated the potential for anti-inflammatory action not typically seen with traditional lung clearing pharmaceuticals [20,21,22,23]. However, these previous studies were unable to determine the mechanism of action by which brevenal reduced lung inflammation.…”

“…Any anti-inflammatory effects would be secondary and synergistic to the primary effect of increasing tracheal mucosal velocity and mucocilliary clearance. Indeed, it has been suggested that general anti-inflammatory effects are a leading reason why brevenal is believed to be superior over current CF treatments [22]. As a treatment for lung clearance, however, brevenal has been stated to be ineffective at doses below 0.1 nM [39], making doses below this less physiologically relevant for either use.…”

“…The choice of doses was based on toxicity studies and previous studies and efficacy of brevenal as a treatment for increasing tracheal mucosal velocity and mucocilliary clearance, as any anti-inflammatory effect would be additive to its use as a CF therapy. Previous studies found efficacy of brevenal from 1 ng/mL (1.52 nM equivalent) to 50 µg/mL (76.22 µM equivalent) [20,21,22,39]. Additionally, brevenal has been found to be ineffective below 1 ng/mL [39].…”

“…During the in vivo investigation of the antagonistic effects of brevenal against brevetoxins, it was discovered that brevenal alone could also attenuate the effects of other inflammatory agents. For example, brevenal has been shown to attenuate neutrophil elastase-induced bronchoconstriction and decrease neutrophil recruitment into the lung [20,21,22]. These results indicate anti-inflammatory effects not typically seen with traditional lung clearing pharmaceuticals [20,21,22,23].…”

“…For example, brevenal has been shown to attenuate neutrophil elastase-induced bronchoconstriction and decrease neutrophil recruitment into the lung [20,21,22]. These results indicate anti-inflammatory effects not typically seen with traditional lung clearing pharmaceuticals [20,21,22,23]. Brevenal has also been found to attenuate PbTx-induced activity and sodium influx in, but not activation of, mast cells, a key immune cell that coordinates allergic responses [24].…”