# Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis.
> 分子状水素はIL-33/ILC2軸の抑制を介して喘息を緩和する


## Abstract

Using an OVA-sensitized asthmatic mouse model and a house dust mite (HDM)-stimulated 16HBE bronchial epithelial cell model, this study examined the effects of hydrogen/oxygen gas mixture on type II airway inflammation. In OVA-challenged mice, serum and bronchoalveolar lavage fluid concentrations of IL-33 and other type II cytokines were markedly elevated; hydrogen administration significantly reduced these levels. NF-κB (p65) and ST2 expression were upregulated by OVA and downregulated by hydrogen. The ILC2 population expanded in asthmatic mice was substantially reduced following hydrogen exposure. Airway epithelial junction proteins E-cadherin and ZO-1, diminished in asthmatic mice, were restored by hydrogen. In HDM-treated 16HBE cells, hydrogen attenuated apoptosis, suppressed IL-33 and ST2 upregulation, and reduced IL-33 promoter activity as measured by dual-luciferase assay. miRNA array profiling identified a distinct set of differentially expressed miRNAs in HDM-exposed cells that were modulated by hydrogen co-treatment. Collectively, these findings indicate that molecular hydrogen suppresses allergen-driven type II inflammation through the IL-33/ILC2 axis.

### Mechanism

Molecular hydrogen suppresses NF-κB (p65) activation, thereby reducing IL-33 promoter activity and ST2 expression, which in turn limits ILC2 expansion and downstream type II inflammatory cytokine production.

## Bibliographic

- **Authors**: Zhang JH, Feng X, Fan Y, Zhu G, Bai C
- **Journal**: Inflamm Res
- **Year**: 2021
- **PMID**: [33852061](https://pubmed.ncbi.nlm.nih.gov/33852061/)
- **DOI**: [10.1007/s00011-021-01459-w](https://doi.org/10.1007/s00011-021-01459-w)
- **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 33852061. https://h2-papers.org/en/papers/33852061
> **Source**: PubMed PMID [33852061](https://pubmed.ncbi.nlm.nih.gov/33852061/)