Circadian rhythms can influence outcomes related to influenza infections

Researchers at Children's Hospital of Philadelphia (CHOP) found that circadian rhythms – the biological clocks of the body – can influence outcomes related to influenza infections, providing clinicians with insight about how biological processes can be used to optimize care for critically ill patients with respiratory viral infections. The findings were recently published in the Journal of Clinical Investigation.

Circadian rhythms are internal biological processes that follow an approximately 24-hour cycle, evolved to allow living organisms to adapt to changes in their environment. Individual organs and cells have their own clocks regulated by circadian rhythms. Most adults are aware that lifestyle choices like shift work and jet lag can disrupt these rhythms and reduce alertness, disrupt sleep-patterns and negatively impact overall well-being. However, it is generally less well known or understood that the outcome of infections can also be directly controlled by the state of circadian rhythms of the host. Understanding these rhythms can therefore provide ways for clinicians to improve clinical interventions and outcomes by timing them to match the endogenous body clock.

When it comes to circadian rhythms and infection, light and mealtime are important "zeitgebers," or external rhythmic cues, that synchronize with other cues in individual organs and cells to support optimal biological function. In previous research, the study team demonstrated that certain times of day are associated with better protection against viruses like influenza, with preclinical findings showing infections during the day had better responses to the infection, but the need for rhythmic external cues that boost body's endogenous clock mechanisms was not known.

"Since influenza affects patients over a period of several days, we were able to test how zeitgebers like light influence this time-of-day-specific protection even after the host sustains the infection," said senior study author Shaon Sengupta, MBBS, MPH, an attending neonatologist in the Division of Neonatology at CHOP whose research focuses on circadian rhythms. "We suspected that sustaining exposure to these rhythmic external cues helps maintain this level of protection after an infection."

Using a preclinical model, the researchers found that disrupting environmental lighting cues – throwing off a typical rest schedule – within a critical window of vulnerability negated the time-of-day-specific protection observed in prior studies. This resulted in a dysregulated immune response, with inflammatory cells accumulating in the lungs during an upper respiratory infection. However, maintaining a rhythmic meal schedule mitigated the adverse effects of disrupted light cycles, suggesting that external cues can compensate for other body clocks that might be disrupted.

Our findings are of particular relevance for hospitalized patients, since circadian disruption due to erratic light-cycling or meal timing are rather prevalent in such settings. Our data suggest that circadian health of the host is a critical determinant of outcomes and may be modified by well-timed environmental cues with potential to drive outcomes in severe respiratory viral infection. Beyond mechanistic insights, our study calls for incorporating circadian-sensitive practices on hospital floors and intensive care units. These may include, but are not limited to, light-cycling and meal-timing interventions as strategies to bolster immune response and hasten recovery."

Shaon Sengupta, MBBS, MPH, senior study author 

This study was supported by the National Institutes of Health grants R01HL155934-01A1 and NHLBI R01HL147472 and a grant from the Raine Medical Research Foundation.