# The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury.
> ブレオマイシン誘発肺傷害マウスにおける水素ガス吸入がマクロファージ極性化・線維化・肺機能に及ぼす影響


## Abstract

Mice received intratracheal bleomycin (1.0 mg/kg) to induce lung injury and were subsequently exposed to 3.2% hydrogen gas in air for 6 hours daily over 7 or 21 days. After 21 days, hydrogen-exposed animals showed significantly higher static compliance (0.056 mL/cmH₂O) compared with air-only controls (0.042 mL/cmH₂O, p=0.02), along with reduced static elastance. At the 7-day time point, mRNA levels of IL-6, IL-4, and IL-13 were markedly lower in hydrogen-exposed mice. Additionally, the proportion of M2-polarized macrophages in the alveolar interstitium was significantly reduced in the hydrogen group (1.1% vs 3.1%, p=0.008). These findings indicate that repeated hydrogen inhalation may restrain persistent inflammatory signaling, limit M2 macrophage accumulation, and thereby attenuate alveolar fibrosis and the decline of respiratory mechanics in bleomycin-induced lung injury.

### Mechanism

Hydrogen inhalation suppressed pro-inflammatory and M2-polarizing cytokines (IL-6, IL-4, IL-13) at the mRNA level and reduced M2-biased macrophage accumulation in the alveolar interstitium, thereby limiting persistent inflammation and subsequent fibrotic remodeling.

## Bibliographic

- **Authors**: Aokage T, Seya M, Hirayama T, Nojima T, Iketani M, Ishikawa M, et al.
- **Journal**: BMC Pulm Med
- **Year**: 2021 (2021-10-31)
- **PMID**: [34719405](https://pubmed.ncbi.nlm.nih.gov/34719405/)
- **DOI**: [10.1186/s12890-021-01712-2](https://doi.org/10.1186/s12890-021-01712-2)
- **PMC**: [PMC8559370](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559370/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 3.2%

## 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 34719405. https://h2-papers.org/en/papers/34719405
> **Source**: PubMed PMID [34719405](https://pubmed.ncbi.nlm.nih.gov/34719405/)