# 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](https://pubmed.ncbi.nlm.nih.gov/37375833/)
- **DOI**: [10.3390/ph16060885](https://doi.org/10.3390/ph16060885)
- **PMC**: [PMC10302845](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302845/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 37375833. https://h2-papers.org/en/papers/37375833
> **Source**: PubMed PMID [37375833](https://pubmed.ncbi.nlm.nih.gov/37375833/)