Macrolide antibiotics improve phagocytic capacity and reduce inflammation in sulfur mustard‐exposed monocytes

Abstract

Sulfur 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. The present study investigated the effects of four FDA‐approved macrolide antibiotics, namely azithromycin, clarithromycin, erythromycin, and roxithromycin, on macrophage chemotactic and phagocytotic function and on inflammatory cytokines/mediators production in vitro using SM‐exposed monocytes. It has been found that chemotaxis 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 expression of iNOS induced by SM exposure was largely inhibited by treatment with macrolides. These data suggest that treatment by macrolide antibiotics following SM inhalation may lead to improved clearance of apoptotic material in the airway and ultimately result in reduced airway inflammation and injury, further suggesting that macrolide antibiotics may serve as potential vesicant respiratory therapeutics. This work was supported by JSTO‐CBD/DTRA Project No. 3.F0003_05_WR_C.