Hydrogen Attenuates Inflammation by Inducing Early M2 Macrophage Polarization in Skin Wound Healing.
水素吸入による早期M2マクロファージ極性化誘導を介した皮膚創傷治癒における炎症抑制
Abstract
Macrophages are central regulators of wound healing, particularly during the inflammatory phase. Using a dorsal full-thickness skin defect mouse model, this study examined the temporal effects of H2 inhalation on macrophage polarization. H2 inhalation promoted M1-to-M2 polarization approximately 2–3 days earlier than observed in standard wound healing (occurring on post-wounding days 2–3), while preserving M1 macrophage functionality. Time-series analyses integrating transcriptomics, peripheral blood cell counts, and cytokine profiling indicated that circulating monocytes serve as a primary source of H2-induced M2 macrophages. Furthermore, the polarization-promoting effects of H2 appeared to extend beyond its known antioxidant properties, suggesting additional mechanistic pathways. These findings indicate that H2 inhalation may reduce wound-associated inflammation by accelerating early macrophage phenotype switching.
Mechanism
H2 inhalation accelerates M1-to-M2 macrophage polarization within 2–3 days post-wounding, with peripheral blood monocytes as the cellular source. The mechanism involves pathways beyond antioxidant activity, reducing inflammatory signaling during the early wound healing phase.
Bibliographic
- Authors
- Zhao PL, Cai ZY, Zhang XQ, Liu M, Xie F, Liu Z, et al.
- Journal
- Pharmaceuticals (Basel)
- Year
- 2023 (2023-06-15)
- PMID
- 37375833
- DOI
- 10.3390/ph16060885
- PMC
- PMC10302845
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
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