title: Altered lung function relates to inflammation in an acute LPS mouse model.
abstract: Preclinical in vivo models of lipopolysaccharide (LPS) -induced acute lung injury are commonly used to recapitulate pathophysiological features of chronic obstructive pulmonary disease and acute exacerbations. The LPS-induced lung inflammation is well described; however, whether the inflammatory response relates temporally to specific alterations in lung function has not been elucidated. We have investigated the effects of acute LPS inhalation in mice up to 96 h post LPS. Quantitation of inflammatory cells and inflammatory mediators in bronchoalveolar lavage fluid and non-invasive and invasive lung function measurements were performed at corresponding time points. The inhibitory effect of the glucocorticoid, budesonide, on LPS-induced lung inflammation and lung function was determined. LPS inhalation induced distinct histopathological changes, and infiltration of inflammatory cells to the lungs peaked at 48 h. At this time point, significantly increased inflammatory mediators and significantly altered lung capacity and mechanics parameters were observed. Budesonide given per os prevented the LPS-induced lung inflammation and lung dysfunction. These results demonstrate a temporal relationship between the peak of inflammatory cell influx and significant impairment of lung function, suggestive of a causative role of inflammation. These results allow better understanding of the functional consequences of lung inflammation in respiratory diseases.
authors.affiliation: Former employees of AstraZeneca R&D, Lund, Sweden. Hanna_fn@bredband.net
authors.forename: Hanna Falk
authors.initials: HF
authors.lastname: Håkansson
authors.forename: Amir
authors.initials: A
authors.lastname: Smailagic
authors.forename: Charlott
authors.initials: C
authors.lastname: Brunmark
authors.forename: Anna
authors.initials: A
authors.lastname: Miller-Larsson
authors.forename: Harbans
authors.initials: H
authors.lastname: Lal
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015656:Respiratory Mechanics / Q000187:drug effects; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides