title: Macrolide antibiotics improve chemotactic and phagocytic capacity as well as reduce inflammation in sulfur mustard-exposed monocytes.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  Chemotaxis and phagocytosis of the monocytes reduced upon exposure to 10microM SM (8.1% and 17.5%, respectively) were restored by treatment with 10microM 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. xiugong.gao@amedd.army.mil
authors.forename: Xiugong
authors.initials: X
authors.lastname: Gao
authors.forename: Radharaman
authors.initials: R
authors.lastname: Ray
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishida
authors.forename: Prabhati
authors.initials: P
authors.lastname: Ray
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009151:Mustard Gas / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002619:Chemical Warfare Agents; D016207:Cytokines; D018836:Inflammation Mediators; D018942:Macrolides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D009151:Mustard Gas