title: 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.
abstract: 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 (H(2)S) donor reduced metabolism with concurrent reduction of lung injury. Here, we hypothesize that prolonged H(2)S infusion is more protective than a short course in endotoxemia with organ failure. Also, as H(2)S has both pro- and anti-inflammatory effects, we explored the effect of H(2)S on interleukin production. Endotoxemia was induced by an intravenous bolus injection of LPS (7.5mg/kg) in mechanically ventilated rats. H(2)S donor NaHS (2mg/kg) or vehicle (saline) was infused and organ injury was determined after either 4 or 8h. A short course of H(2)S infusion was associated with reduction of lung and kidney injury. Prolonged infusion did not enhance protection. Systemically, infusion of H(2)S 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 H(2)S 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 H(2)S infusion reduced organ injury during endotoxemia, at least in part via upregulation of IL-10.
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands. h.aslami@amc.uva.nl
authors.forename: Hamid
authors.initials: H
authors.lastname: Aslami
authors.forename: Charlotte J P
authors.initials: CJ
authors.lastname: Beurskens
authors.forename: Friso M
authors.initials: FM
authors.lastname: de Beer
authors.forename: Maria T
authors.initials: MT
authors.lastname: Kuipers
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Maria A
authors.initials: MA
authors.lastname: Hegeman
authors.forename: Koen F
authors.initials: KF
authors.lastname: Van der Sluijs
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Juffermans
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; D001219:Aspartate Aminotransferases; D006862:Hydrogen Sulfide