# Hydrogen Gas Therapy Attenuates Inflammatory Pathway Signaling in Septic Mice.
> 敗血症マウスにおける水素ガス吸入による炎症シグナル経路の抑制


## Abstract

Using a cecal ligation and puncture (CLP) sepsis model in 9-week-old male C57BL/6 mice, this study examined the effects of continuous 7% H2 gas inhalation on survival, systemic inflammation, and multi-organ gene expression. The 7-day survival rate reached 75% in H2-inhaled mice versus 40% in controls (P < 0.05). Serum interleukin-6 and tumor necrosis factor-α concentrations were reduced at 24 hours post-CLP, and blood glucose levels were better maintained in H2-exposed animals. RNA sequencing of liver, intestine, and lung tissue, analyzed via Ingenuity Pathway Analysis, revealed suppression of acute phase response signaling and STAT3 pathways in the liver and intestine. Upstream regulator genes including CD14 in the liver and multiple cytokine receptor genes in the intestine and lungs showed significantly decreased expression following H2 inhalation, providing mechanistic insight into how molecular hydrogen modulates the inflammatory cascade in sepsis.

### Mechanism

H2 inhalation downregulates CD14 gene expression in the liver and cytokine receptor genes in the intestine and lungs, leading to inactivation of acute phase response signaling and the STAT3 pathway, thereby attenuating systemic inflammatory responses in septic mice.

## Bibliographic

- **Authors**: Matsuura H, Matsumoto H, Okuzaki D, Shimizu K, Ogura H, Ebihara T, et al.
- **Journal**: J Surg Res
- **Year**: 2021
- **PMID**: [33639371](https://pubmed.ncbi.nlm.nih.gov/33639371/)
- **DOI**: [10.1016/j.jss.2021.01.022](https://doi.org/10.1016/j.jss.2021.01.022)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 7%

## 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 33639371. https://h2-papers.org/en/papers/33639371
> **Source**: PubMed PMID [33639371](https://pubmed.ncbi.nlm.nih.gov/33639371/)