Protective anti-inflammatory effects of photobiomodulation with Red/NIR light in a mouse model of LPS-induced systemic and brain inflammation

Abstract

Abstract Background There is an urgent need for therapeutic approaches that can prevent or limit neuroinflammatory processes and prevent neuronal degeneration. Photobiomodulation (PBM), the therapeutic use of specific wavelengths of light, is a safe approach shown to have anti-inflammatory effects. The current study was aimed at evaluating the effects of PBM on LPS-induced peripheral and central inflammation in mice to assess the potential of PBM as an anti-inflammatory treatment. Methods Effects of PBM were evaluated in group-housed C57BL/6J mice. Mice were divided into three groups: (a) a control group receiving no PBM, (b) a group receiving PBM utilizing red/NIR light at 640 and 880 nm (RL), and (c) a group receiving RL with a 40 Hz gamma frequency flicker (RLG). PBM was administered over 12 days (5 days per week for 2 weeks; no treatment on days 6 and 7). Each PBM treatment was 30 minutes. On day 11, mice were dosed by intraperitoneal injection with either vehicle or LPS (1 mg/kg). Brain and plasma samples were collected on day 12, 24 hours after LPS/vehicle injection and after one final PBM treatment. Samples were investigated for inflammatory responses, using qPCR to measure mRNA expression and western blot and Luminex assays to measure protein expression levels. Results Analysis by qPCR revealed that PBM with RL and RLG significantly reduced the gene expression of IL-18, while RL also reduced IL-6 expression in the brain. Luminex analyses confirmed that LPS induced the expected robust upregulation of cytokines in plasma and the brain. In plasma, RL and RLG modulated LPS induction of IL-10, IL-1β, IL-22, and IL-7Rα. In addition, RL modulated LPS-induction of IL-18 and MIP-1β, while RLG modulated IP-10, IFN-γ, RANTES, MCP-1, IL-2Rα, and BTC. In hippocampal-containing brain tissue, RL and RLG prevented the LPS-induction of ST2 and IFN-α, while RLG also inhibited the LPS-induction of sRANKL, MCP-1, and IL-15. Conclusions Daily, 30-minute PBM treatment with RL or RLG for 10 days prior to an LPS challenge had anti-inflammatory effects in C57BL/6J mice, in the brain and systemically. RL, independent of gamma flicker, provided robust anti-inflammatory effects, and the addition of gamma flicker further potentiated these effects. Overall, these results show the potential of PBM as an experimental anti-inflammatory treatment. Future studies will be needed to understand the mechanism of action, safety, and effectiveness of PBM.