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

作者：Aslami Hamid^*; Beurskens Charlotte J P; de Beer Friso M; Kuipers Maria T; Roelofs Joris J T H; Hegeman Maria A; Van der Sluijs Koen F; Schultz Marcus J; Juffermans Nicole P

来源：Cytokine, 2013, 61(2): 614-621.

DOI：10.1016/j.cyto.2012.11.018

• Acute respiratory distress syndrome
• Sepsis
• Multiple organ failure
• Inflammation
• Interleukin 10

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. %26lt;br%26gt;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-alpha, 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-alpha levels and increased IL-10 levels. Co-incubation with a neutralizing IL-10 antibody partly abrogated the decrease in TNF-alpha levels. In conclusion, a short course of H2S infusion reduced organ injury during endotoxemia, at least in part via upregulation of IL-10.

• 出版日期2013-2