650 nm red-light therapy attenuates sepsis-induced acute lung injury via adiponectin-mediated immune-metabolic reprogramming.
Level 5 - mechanism / opinion, no new human data
Preclinical animal (mouse CLP model) and in vitro mechanistic laboratory study.
PubMed 41659861 · doi:10.3389/fimmu.2026.1710363
What was done
Cecal ligation and puncture (CLP) was used to induce septic acute lung injury (ALI) in mice. Animals received 650 nm red-light photobiomodulation (PBM) for 10 minutes every 6 hours (three sessions over 24 hours). Investigators assessed survival, lung edema, histology, serum cytokines, lung chemokine/cytokine profiles via a 23-plex Luminex panel, and immune cell subsets via flow cytometry, immunohistochemistry, and 3D cryo-fMOST. The role of adiponectin signaling was evaluated using AdipoR1 siRNA in vivo and in lipopolysaccharide-stimulated RAW264.7 macrophages assessing ATP production, mitochondrial reactive oxygen species, and mitochondrial membrane potential.
What was found
The abstract reports qualitative directions of effect without exact numeric values. PBM extended survival, reduced pulmonary edema, improved lung histology, and decreased systemic TNF-α, IL-6, IL-1β, and MCP-1. Luminex profiling demonstrated broad suppression of inflammatory mediators (including G-/GM-CSF, IL-1 family, IL-6, IL-12, IL-17A, TNF-α, CXCL1, CCL2/3/4/5) and increased IL-4, IL-10, and IL-13. Cryo-fMOST and flow cytometry showed reduced infiltration of CCR2+/CD86+ inflammatory myeloid cells alongside an increase in CX3CR1+/CD206+ reparative macrophages. Adiponectin levels increased in serum, bronchoalveolar lavage fluid, and lung tissue. In vitro, PBM dose-dependently reduced inflammatory cytokines, lowered mitochondrial ROS, restored ATP, and preserved mitochondrial membrane potential. Silencing AdipoR1 abolished these therapeutic effects both in vivo and in vitro.
Why it matters
This study identifies an adiponectin-AdipoR1-dependent pathway through which red-light photobiomodulation modulates myeloid cell phenotype and preserves mitochondrial function in preclinical sepsis.
Limits
The study is entirely preclinical, relying on a mouse CLP model and an immortalized macrophage cell line; human translation cannot be assumed. The abstract provides no specific quantitative metrics, sample sizes, or survival statistics. Significant anatomical differences in light penetration between small rodents and human thorax represent a major translational barrier.