A short course of infusion of a hydrogen sulfide-donor attenuates endotoxemia induced organ injury via stimulation of anti-inflammatory pathways,with no additional protection from prolonged infusion

Organ failure is associated with increased mortality and morbidity in patients with systemic inflammatory response syndrome. Previously, we showed that a short course of infusion of a hydrogen sulfide (H₂S) donor reduced metabolism with concurrent reduction of lung injury. Here, we hypothesize that prolonged H₂S infusion is more protective than a short course in endotoxemia with organ failure. Also, as H₂S has both pro- and anti-inflammatory effects, we explored the effect of H₂S on interleukin production.Endotoxemia was induced by an intravenous bolus injection of LPS (7.5 mg/kg) in mechanically ventilated rats. H₂S donor NaHS (2 mg/kg) or vehicle (saline) was infused and organ injury was determined after either 4 or 8 h. A short course of H₂S infusion was associated with reduction of lung and kidney injury. Prolonged infusion did not enhance protection. Systemically, infusion of H₂S increased both the pro-inflammatory response during endotoxemia, as demonstrated by increased TNF-α levels, as well as the anti-inflammatory response, as demonstrated by increased IL-10 levels. In LPS-stimulated whole blood of healthy volunteers, co-incubation with H₂S had solely anti-inflammatory effects, resulting in decreased TNF-α levels and increased IL-10 levels. Co-incubation with a neutralizing IL-10 antibody partly abrogated the decrease in TNF-α levels. In conclusion, a short course of H₂S infusion reduced organ injury during endotoxemia, at least in part via upregulation of IL-10.