(1602) Sleep Fragmentation Amplifies Inflammation in Mice With Acute Lung Injury

Introduction: It is well established that critically ill patients experience sleep dysregulation in the ICU setting although the clinical significance of poor sleep quality is not fully known. Acute lung injury (ALI) is an inflammatory respiratory disorder resulting in significant morbidity and mortality. Recently, a model of sleep fragmentation (SF) characterizing the critical care setting was created with EEG data showing decreased deep sleep in mice exposed to these conditions. However, this model has not yet been characterized in terms of phenotype correlation with injury-associated inflammation, timing, or cellular environment. This study aims to investigate the inflammatory effects of SF in mice with ALI. We hypothesize that mice with ALI who are exposed to SF conditions will display increased inflammatory characteristics.

Methods: SF is produced by intermittently shaking mice in addition to disrupting their light/dark cycle. ALI is induced using intratracheal instillation of Streptococcus pneumoniae. Mice are observed for 7 days during which peak injury and resolution of ALI occur. Blood, bronchoalveolar lavage (BAL) fluid, lung, and spleen are collected and analyzed to examine levels of different populations of inflammatory cells and cytokines.

Results: ALI from direct Streptococcus pneumoniae instillation demonstrates increased levels of inflammatory cells in both lung and BAL samples. Independently of ALI, SF studies show a predominance of inflammatory cells in the SF group compared to the control group. Inflammatory cells in SF mice remain elevated throughout the course of the study. Preliminary studies combining ALI and SF show an additive effect on inflammation and delayed resolution of injury with cell counts and inflammatory markers not returning to baseline at day 7 post-infection. Ongoing studies include imaging via CT scanning to correlate inflammatory status with clinical features.

Conclusions: These results demonstrate the importance of appropriate sleep in the resolution of inflammation at the cellular level. SF mice experience a larger influx of inflammatory cells at the peak of infection as well as a delay in complete injury resolution. This demonstrates that improving sleep quality can reduce inflammation in critically ill patients thereby aiding their recovery.