Macrolide antibiotics improve chemotactic and phagocytic capacity as well as reduce inflammation in sulfur mustard-exposed monocytes

BackgroundSulfur mustard (SM) inhalation causes apoptosis and death of airway epithelial cells as well as inflammation in the airway. Efficient clearance of the cell debris by alveolar macrophages is necessitated to reduce the inflammation. Macrolide antibiotics have been reported to have anti-inflammatory properties by modulating the production of proinflammatory cytokines and mediators, and by improving macrophage functions. The present study investigated the effects of four commonly used macrolide antibiotics, namely azithromycin, clarithromycin, erythromycin, and roxithromycin, on chemotactic and phagocytotic function and on inflammatory cytokines/mediators production in vitro in SM-exposed monocyte THP-1 cells.ResultsChemotaxis and phagocytosis of the monocytes reduced upon exposure to 10 μM SM (8.1% and 17.5%, respectively) were restored by treatment with 10 μM of any of the four macrolides. Overexpression of inflammatory cytokines following SM exposure was decreased by 50–70% with macrolide treatment. Similarly, exaggerated iNOS expression and nitric oxide (NO) production induced by SM exposure was largely inhibited by treatment with macrolides.ConclusionThe data demonstrate that macrolide antibiotics were effective in improving the degenerated chemotactic and phagocytotic functions of monocytes following SM exposure, and in reducing SM-induced overproduction of proinflammatory cytokines and mediators. Thus, treatment with macrolide antibiotics may lead to improved clearance of apoptotic material in the airway and ultimately result in reduced airway inflammation and injury caused by SM inhalation, suggesting that macrolide antibiotics may serve as potential vesicant respiratory therapeutics.