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Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice.

Faller S, Zimmermann KK, Strosing KM, Engelstaedter H, Buerkle H, Schmidt R, Spassov SG, Hoetzel A - Med Gas Res (2012)

Bottom Line: The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality.The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo.In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Hugstetter Str, 55, D-79106, Freiburg, Germany. simone.faller@uniklinik-freiburg.de.

ABSTRACT

Background: Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury.

Methods: C57BL/6 N mice received lipopolysaccharide (LPS) intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL) fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance.

Results: Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

Conclusion: Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.

No MeSH data available.


Related in: MedlinePlus

Effect of LPS and hydrogen sulfide inhalation on systemic inflammation. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Blood samples were withdrawn by intracardiac punctation. Myeloperoxidase (MPO, A) and IL-1β (B) contents were quantified by ELISA in serum. Graphs represent means ± SEM, n = 6-8/group. ANOVA on Ranks (Dunn`s posthoc test), #P < 0.05 vs. PBS + H2S group.
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Figure 4: Effect of LPS and hydrogen sulfide inhalation on systemic inflammation. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Blood samples were withdrawn by intracardiac punctation. Myeloperoxidase (MPO, A) and IL-1β (B) contents were quantified by ELISA in serum. Graphs represent means ± SEM, n = 6-8/group. ANOVA on Ranks (Dunn`s posthoc test), #P < 0.05 vs. PBS + H2S group.

Mentions: We finally questioned whether intranasal application of LPS would also induce systemic inflammation and whether H2S would exert any systemic effects. As a marker for neutrophil activity we determined the concentration of the MPO glycoprotein in serum [23,26]. In the present study, LPS treatment clearly increased serum MPO release. H2S inhalation tended to reduce MPO levels, irrespective of the mode of additional PBS- or LPS-treatment (Figure 4A). Similar results were obtained by analyzing serum IL-1β levels (Figure 4B). Our findings compliment the results of two previous studies, where LPS-induced systemic inflammation (e.g., plasma nitrite/nitrate levels, pro-inflammatory cytokine release) was also clearly prevented by H2S inhalation [23,29]. However, on the basis of our results, we cannot clearly decipher, whether i.n. LPS directly induced a systemic inflammation or whether the inflammatory response observed resulted from lung injury. Therefore two scenarios concerning the role of H2S appear possible: (1) H2S inhalation may directly inhibit lung and systemic inflammation, or (2) H2S inhalation may primarily inhibit lung inflammatory responses, secondary preventing a systemic inflammation. Either way, our data suggest that H2S inhalation has the potential to inhibit both local as well as systemic inflammatory responses to septic insults.


Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice.

Faller S, Zimmermann KK, Strosing KM, Engelstaedter H, Buerkle H, Schmidt R, Spassov SG, Hoetzel A - Med Gas Res (2012)

Effect of LPS and hydrogen sulfide inhalation on systemic inflammation. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Blood samples were withdrawn by intracardiac punctation. Myeloperoxidase (MPO, A) and IL-1β (B) contents were quantified by ELISA in serum. Graphs represent means ± SEM, n = 6-8/group. ANOVA on Ranks (Dunn`s posthoc test), #P < 0.05 vs. PBS + H2S group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: Effect of LPS and hydrogen sulfide inhalation on systemic inflammation. As controls, mice received phosphate buffered saline (PBS, intranasally) and were kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). LPS-treated mice (LPS treatment, i.n.) were either kept in room air or in 80 ppm H2S for 6 h (plus 1 h pretreatment). Blood samples were withdrawn by intracardiac punctation. Myeloperoxidase (MPO, A) and IL-1β (B) contents were quantified by ELISA in serum. Graphs represent means ± SEM, n = 6-8/group. ANOVA on Ranks (Dunn`s posthoc test), #P < 0.05 vs. PBS + H2S group.
Mentions: We finally questioned whether intranasal application of LPS would also induce systemic inflammation and whether H2S would exert any systemic effects. As a marker for neutrophil activity we determined the concentration of the MPO glycoprotein in serum [23,26]. In the present study, LPS treatment clearly increased serum MPO release. H2S inhalation tended to reduce MPO levels, irrespective of the mode of additional PBS- or LPS-treatment (Figure 4A). Similar results were obtained by analyzing serum IL-1β levels (Figure 4B). Our findings compliment the results of two previous studies, where LPS-induced systemic inflammation (e.g., plasma nitrite/nitrate levels, pro-inflammatory cytokine release) was also clearly prevented by H2S inhalation [23,29]. However, on the basis of our results, we cannot clearly decipher, whether i.n. LPS directly induced a systemic inflammation or whether the inflammatory response observed resulted from lung injury. Therefore two scenarios concerning the role of H2S appear possible: (1) H2S inhalation may directly inhibit lung and systemic inflammation, or (2) H2S inhalation may primarily inhibit lung inflammatory responses, secondary preventing a systemic inflammation. Either way, our data suggest that H2S inhalation has the potential to inhibit both local as well as systemic inflammatory responses to septic insults.

Bottom Line: The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality.The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo.In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Hugstetter Str, 55, D-79106, Freiburg, Germany. simone.faller@uniklinik-freiburg.de.

ABSTRACT

Background: Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury.

Methods: C57BL/6 N mice received lipopolysaccharide (LPS) intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL) fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance.

Results: Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation.

Conclusion: Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.

No MeSH data available.


Related in: MedlinePlus