Blue light reduces organ injury during critical illness
Author(s):
Du Yuan, University of Pittsburgh; Richard Collage, University of Pittsburgh; Hai Huang, University of Pittsburgh; Xianghong Zhang, University of Pittsburgh; Benjamin Kautza, University of Pittsburgh; Brian Zuckerbraun, University of Pittsburgh School of Medicine; Derek Angus, University of Pittsburgh; Allan Tsung, UPMC Liver Cancer Center; Matthew Rosengart, University of Pittsburgh
Background: The current biological evidence suggests that the photoperiodicity of light profoundly influences the physiologic capacity with which an organism responds to stress. However, the ramifications of light intensity and wavelength on the course of critical illness remain to be determined.
Hypothesis: We hypothesized that a light of optimal spectrum and illuminance can be identified and broadly applied to modify the biology of critical illness.
Methods: Mice (C57BL, 12 weeks) were assigned to one of 3 models of septic or sterile insult: 1) 1 cm ligation, 21-gauge double puncture CLP; 2) segmental hepatic I/R; and 3) unilateral kidney I/R. For 24 hours prior to I/R or after CLP, mice were exposed to one of 3 lighting conditions: 1) 1400 lumens BLUE (peak 442 nm) spectrum; 2) 1400 lumens, RED (peak 617 nm) spectrum; or 3) AMBIENT white fluorescent light. For CLP, peritoneal lavage fluid and blood were collected to determine bacteria clearance. Acute kidney injury (AKI) was quantified using serum Cystatin C concentration. Systemic inflammation was quantified by assaying serum IL-6, IL-10 and TNFa concentrations. For I/R, liver injury was quantified by assaying serum ALT concentration, and AKI by Cystatin C. Serum HMGB1 was measured by immunoblot. Organs were subjected to H & E to quantify the degree of cellular necrosis. Organ myeloperoxidase (MPO) activity was quantified to assess neutrophil concentration. These experiments were repeated using Vsx2or-J/J mice, which undergo optic nerve degeneration.
Results: Compared with RED or AMBIENT light, exposure to BLUE light after CLP enhanced peritoneal bacterial clearance (p=0.07), reduced bacteremia (p<0.05) and reduced inflammation: IL-6 (p<0.05), IL-10 (p<0.05) and TNFa (p<0.05). This correlated with reduced AKI and Cystatin C (p=0.06). BLUE light prior to I/R reduced liver and kidney injury: ALT (p<0.05) and Cystatin C (p<0.05) . In both I/R models BLUE light reduced organ neutrophil influx and MPO (p<0.05), cellular necrosis (p<0.05) and the release of HMGB1 (p<0.05), a key mediator in the pathogenesis of I/R. The protection afforded by BLUE light occurred independent of significant alterations in melatonin or corticosterone concentrations; yet, did involve an optic pathway, as mice experiencing optic nerve degeneration were not protected.
Conclusions: These data suggest that high illuminance BLUE spectrum light can reduce organ injury in critical illness by comparison to RED spectrum or standard low illuminance, ambient, white fluorescent light.