Effects of age on the synergistic interactions between lipopolysaccharide and mechanical ventilation in mice.

Publication Type:

Journal Article


American journal of respiratory cell and molecular biology, Volume 43, Issue 4, p.475-86 (2010)


2010, Aging, Animals, Center-Authored Paper, Clinical Research Division, Cluster Analysis, Cytokines, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Lipopolysaccharides, lung, Male, MICE, Mice, Inbred C57BL, Multigene Family, Neutrophils, Permeability, Pneumonia, Principal Component Analysis, Respiration, Artificial, Transcription, Genetic


Children have a lower incidence and mortality from acute lung injury (ALI) than adults, and infections are the most common event associated with ALI. To study the effects of age on susceptibility to ALI, we investigated the responses to microbial products combined with mechanical ventilation (MV) in juvenile (21-d-old) and adult (16-wk-old) mice. Juvenile and adult C57BL/6 mice were treated with inhaled Escherichia coli 0111:B4 lipopolysaccharide (LPS) and MV using tidal volume = 15 ml/kg. Comparison groups included mice treated with LPS or MV alone and untreated age-matched control mice. In adult animals treated for 3 hours, LPS plus MV caused synergistic increases in neutrophils (P < 0.01) and IgM in bronchoalveolar lavage fluid (P = 0.03) and IL-1β in whole lung homogenates (P < 0.01) as compared with either modality alone. Although juvenile and adult mice had similar responses to LPS or MV alone, the synergistic interactions between LPS and MV did not occur in juvenile mice. Computational analysis of gene expression array data suggest that the acquisition of synergy with increasing age results, in part, from the loss of antiapoptotic responses and the acquisition of proinflammatory responses to the combination of LPS and MV. These data suggest that the synergistic inflammatory and injury responses to inhaled LPS combined with MV are acquired with age as a result of coordinated changes in gene expression of inflammatory, apoptotic, and TGF-β pathways.