Molecular hydrogen potentiates hypothermia and prevents hypotension and fever in LPS-induced systemic inflammation.

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.