# Molecular hydrogen potentiates hypothermia and prevents hypotension and fever in LPS-induced systemic inflammation.
> LPS誘発全身性炎症モデルにおける分子状水素の体温調節・心血管・炎症パラメータへの影響


## Abstract

Male Wistar rats (250–300 g) received intravenous LPS at 0.1 or 1.5 mg/kg to induce mild or severe systemic inflammation, followed by 360-minute inhalation of 2% H₂ gas. Deep body temperature was monitored via intraperitoneally implanted dataloggers. Under mild inflammation, H₂ inhalation suppressed plasma TNF-α and IL-6 surges, elevated the anti-inflammatory cytokine IL-10, and prevented fever. Under severe inflammation, H₂ potentiated hypothermia and prevented both fever and hypotension; these outcomes coincided with reduced plasma nitric oxide production, decreased TNF-α and IL-1β levels, and lower prostaglandin E₂ (PGE₂) concentrations in both plasma and hypothalamus. H₂ had no measurable effect on cardiovascular, inflammatory, or thermoregulatory parameters in saline-treated control animals. The findings indicate that H₂ modulates febrile and hemodynamic responses in systemic inflammation through suppression of pro-inflammatory mediators and hypothalamic PGE₂ signaling.

### Mechanism

H₂ inhalation reduces plasma nitric oxide production and suppresses pro-inflammatory mediators (TNF-α, IL-1β, PGE₂) while elevating IL-10, thereby downregulating hypothalamic febrile signaling and attenuating thermoregulatory and hemodynamic dysregulation during systemic inflammation.

## Bibliographic

- **Authors**: Saramago EA, Borges GS, Singolani-Jr CG, Nogueira JE, Soriano RN, Cárnio EC, et al.
- **Journal**: Brain Behav Immun
- **Year**: 2019
- **PMID**: [30261305](https://pubmed.ncbi.nlm.nih.gov/30261305/)
- **DOI**: [10.1016/j.bbi.2018.09.027](https://doi.org/10.1016/j.bbi.2018.09.027)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 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 30261305. https://h2-papers.org/en/papers/30261305
> **Source**: PubMed PMID [30261305](https://pubmed.ncbi.nlm.nih.gov/30261305/)