Intrapulmonary delivery of ethyl pyruvate attenuates lipopolysaccharide- and lipoteichoic acid-induced lung inflammation in vivo.
Ethyl pyruvate (EP) is a stable pyruvate derivative that has been shown to exert anti-inflammatory effects in various models of systemic inflammation including endotoxemia. We here sought to determine the local effects of EP, after intrapulmonary delivery, in models of lung inflammation induced by instillation via the airways of either lipopolysaccharide (LPS, a constituent of the gram-negative bacterial cell wall) or lipoteichoic acid (LTA, a component of the gram-positive bacterial cell wall). For this, we first established that EP dose dependently reduced the responsiveness of mouse MH-S alveolar macrophages and mouse MLE-15 and MLE-12 respiratory epithelial cells to stimulation with LPS or LTA in vitro. We then showed that intranasal administration of EP dose dependently inhibited tumor necrosis factor alpha release in bronchoalveolar lavage fluid of mice challenged with either LPS or LTA via the airways. Moreover, EP reduced the recruitment of neutrophils into the bronchoalveolar space after either LPS or LTA administration. These data suggest that intrapulmonary delivery of EP diminishes lung inflammation induced by LPS or LTA, at least in part by targeting alveolar macrophages and respiratory epithelial cells.
van Zoelen
Marieke A D
MA
Center for Infection and Immunity Amsterdam, The Netherlands. M.A.vanZoelen@amc.uva.nl
de Vos
Alex F
AF
Larosa
Gregory J
GJ
Draing
Christian
C
von Aulock
Sonja
S
van der Poll
Tom
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005421:Flavoring Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011773:Pyruvates / Q000494:pharmacology*; D013682:Teichoic Acids / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005421:Flavoring Agents; D008070:Lipopolysaccharides; D011773:Pyruvates; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; C009900:lipoteichoic acid