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
- DOI
- 10.1186/s12890-021-01712-2
- PMC
- PMC8559370
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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