ICU-Associated Sleep Fragmentation Results in Delayed Lung Injury Recovery Following Pneumonia

Background: Sleep has long been linked to proper immune system function. Previous studies have shown poor sleep is associated with increased rates of upper respiratory infections; suggesting increased susceptibility to or worsened response to infections. Patients in the ICU experience markedly disrupted and poor sleep. We created a murine model of ICU-associated sleep fragmentation and aimed to explore the consequences of this level of disrupted sleep on the response to and recovery from pneumonia. Methods: Sleep fragmentation (SF) was induced in wildtype mice using an orbital shaker. After SF, lungs and blood were harvested and assessed with flow cytometry for changes in the immune cell landscape. To assess susceptibility to pneumonia, SF mice were infected with S. pneumoniae (PNA). Injury was measured by weight change, lung wet-to-dry (W/D) weight ratio, bronchoalveolar lavage fluid (BALF) cell count, cell differential, and bacterial CFU. Results: SF exposure alone resulted in fewer total lung cells including key immune cells. Additionally, there was a reduction in the cytokine response. To test susceptibility to infection, mice were exposed to SF and then PNA. While mice exposed to PNA after SF experienced more weight loss by peak injury on day 2 (D2), there was no change in W/D ratios or BALF cell counts compared to PNA alone. To test the impact of SF on recovery from PNA, mice were exposed to SF one day after infection. These mice saw slower weight recovery, increased BALF cell counts and higher W/D weights on D4 and D7, but not on D2. Interestingly, mice exposed to SF after PNA had decreased BALF lymphocytes and higher lung CFUs at D4. Conclusion: While SF-induced decrease in immune cells and cytokine response would suggest reduced ability to respond to infection and more susceptible to injury from pneumonia, this is not reflected in markers of lung injury, W/D ratios or BALF cell counts, at time point of peak injury. Instead, it appears that SF delays recovery from pneumonia. Our data suggests delayed recovery may be a result of decreased T-regulatory cell recruitment and/or delayed clearance of bacteria. Funding support from Department of Defense: W81XWH2110020; and NHLBI: R01HL133413 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.