The anti-inflammatory effects of photobiomodulation are mediated by cytokines: Evidence from a mouse model of inflammation

Abstract

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 its potential as an anti-inflammatory treatment. Daily, 30-min treatment of mice with red/NIR light (RL) or RL with a 40 Hz gamma frequency flicker for 10 days prior to LPS challenge showed anti-inflammatory effects in the brain and systemically. PBM downregulated LPS induction of key proinflammatory cytokines associated with inflammasome activation, IL-1β and IL-18, and upregulated the anti-inflammatory cytokine, IL-10. RL provided robust anti-inflammatory effects, and the addition of gamma flicker potentiated these effects. Overall, these results demonstrate the potential of PBM as an anti-inflammatory treatment that acts through cytokine expression modulation.

Keywords: light therapy; lipopolysaccharide (LPS); neurodegenerative disorders; neuroinflammation; photobiomodulation (PBM); systemic inflammation.

Figure 1

Experimental design. Photobiomodulation (PBM) was administered daily, for 30 min per day, on days 1 through 5 and days 8 through 12. On day 11, mice received either LPS (1 mg/kg) or vehicle injection, IP, 30 min after PBM. On day 12, mice received a final PBM treatment before tissue was collected at 24 hrs after LPS. Luminex, qPCR and western blot assays were performed on brain and plasma samples.

Figure 2

Apparatus setup. Auragen light therapy units contain a matrix of LEDs, which consists of an array of three different types of LED bulbs that can emit light either at 640 nm (red), 880 nm (NIR), and 465 nm (blue turquoise), respectively.

Figure 3

Log2 fold change of plasma cytokines measured in the Luminex assay depicts the effects of (A) red light, (B) red light gamma, and (C) LPS relative to no light + vehicle, as well as effects of (D) red light and (E) red light gamma relative to no light + LPS. Data are presented as mean ± SEM. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, ^****p < 0.0001.

Figure 4

Log2 fold change of cytokines in hippocampal-containing brain tissue measured in the Luminex assay depicts the effects of (A) red light, (B) red light gamma, and (C) LPS relative to no light + vehicle, as well as effects of (D) red light and (E) red light gamma relative to no light + LPS. Data are presented as mean ± SEM. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, ^****p < 0.0001.

Figure 5

RT-qPCR analysis of select markers in hippocampus-containing brain tissue. There was significant downregulation of IL-18, CD68, and IL-6 in the RL + LPS and RLG + LPS groups, when compared to the NL + LPS group. In addition, when compared with the NL + Veh group, there was a significant downregulation of IL-18 in both the RL + Veh and the RLG + Veh groups, as well as a downregulation of IL-6 in the RL + Veh group. Upregulation of TNF-α and IL-1β was consistent with an inflammatory response in the NL + LPS group, when compared to the NL + Veh group. Data are presented as mean ± SEM. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, ^****p < 0.0001.