by Lewis, Anthony J.;
Zhang, Xianghong; Griepentrog, John E.; Yuan, Du; Collage, Richard D.; Waltz,
Paul K.; Angus, Derek C.; Zuckerbraun, Brian S.; Rosengart, Matthew R.
Objectives: The
physiology of nearly all mammalian organisms are entrained by light and exhibit
circadian rhythm. The data derived from animal studies show that light
influences immunity, and these neurophysiologic pathways are maximally
entrained by the blue spectrum. Here, we hypothesize that bright blue light
reduces acute kidney injury by comparison with either bright red or standard,
white fluorescent light in mice subjected to sepsis. To further translational
relevance, we performed a pilot clinical trial of blue light therapy in human
subjects with appendicitis. Design: Laboratory animal research, pilot human
feasibility trial. Setting: University basic science laboratory and tertiary
care hospital. Subjects: Male C57BL/6J mice, adult (> 17 yr) patients with
acute appendicitis. Interventions: Mice underwent cecal ligation and puncture
and were randomly assigned to a 24-hour photoperiod of bright blue, bright red,
or ambient white fluorescent light. Subjects with appendicitis were randomized
to receive postoperatively standard care or standard care plus high-illuminance
blue light. Measurements and Main Results: Exposure to bright blue light
enhanced bacterial clearance from the peritoneum, reduced bacteremia and
systemic inflammation, and attenuated the degree of acute kidney injury. The
mechanism involved an elevation in cholinergic tone that augmented tissue
expression of the nuclear orphan receptor REV-ERBα and occurred independent of
alterations in melatonin or corticosterone concentrations. Clinically, exposure
to blue light after appendectomy was feasible and reduced serum interleukin-6
and interleukin-10 concentrations. Conclusions: Modifying the spectrum of light
may offer therapeutic utility in sepsis.
