Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis

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. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by a Basic/Translational Research Training Fellowship Grant awarded by the Surgical Infection Society (to Dr. Rosengart), R01 GM082852 (to Dr. Rosengart), R01 GM116929 (to Dr. Rosengart), and T32GM008516 (to Dr. Lewis) from the National Institutes of Health. Drs. Lewis, Griepentrog, Zuckerbraun, and Rosengart received support for article research from the National Institutes of Health. Dr. Zuckerbraun disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: rosengartmr@upmc.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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