Background <p>Pneumonia caused by <i>Streptococcus pneumoniae</i> remains a major global health concern, leading to significant morbidity and mortality. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide with known anti-inflammatory and pro-resolving properties, but its therapeutic potential in bacterial pneumonia is not fully understood.</p> Purpose <p>This study aimed to investigate whether Ang-(1-7) could reduce inflammation, improve bacterial clearance, and enhance survival in a murine model of pneumococcal pneumonia, alone or in combination with the antibiotic ceftriaxone.</p> Methods <p>A mouse model of <i>S. pneumoniae</i> pneumonia was used to evaluate the effects of Ang-(1-7). Mice received Ang-(1-7) treatment after infection, either alone or combined with ceftriaxone. Outcomes included leukocyte infiltration, pulmonary edema, lung tissue damage, cytokine production (TNF-α, IL-6, CXCL-1), bacterial load in bronchoalveolar lavage and blood, survival analysis, bone marrow-derived macrophage phagocytosis assays, and expression of lung barrier–associated genes.</p> Results <p>Ang-(1-7) reduced leukocyte infiltration, pulmonary edema, and lung tissue injury, and decreased pro-inflammatory cytokine levels. Treatment improved bacterial clearance in both lungs and bloodstream and increased survival in infected mice. Importantly, combining Ang-(1-7) with ceftriaxone further enhanced survival, even when treatment initiation was delayed. Mechanistically, Ang-(1-7) increased macrophage phagocytic activity and upregulated genes associated with lung barrier integrity.</p> Conclusion <p>Ang-(1-7) decreased inflammation, improved bacterial clearance, and enhanced survival in severe pneumococcal pneumonia. Its combination with ceftriaxone produced additive benefits, supporting Ang-(1-7) as a promising adjuvant therapeutic strategy in this infectious condition</p>

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Angiotensin-(1-7) treatment improves pneumonia and prevents sepsis caused by pneumococcal infection

  • Eliza Mathias Melo,
  • Izabela Galvão,
  • Franciel Batista Felix,
  • Fernanda Medeiros Vale Magalhães,
  • Flavia Rago,
  • Marina Gomes Machado,
  • Fernando Roque Ascenção,
  • Maria José Campagnole-Santos,
  • Robson Augusto Souza dos Santos,
  • Geovanni Dantas Cassali,
  • Mauro Martins Teixeira

摘要

Background

Pneumonia caused by Streptococcus pneumoniae remains a major global health concern, leading to significant morbidity and mortality. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide with known anti-inflammatory and pro-resolving properties, but its therapeutic potential in bacterial pneumonia is not fully understood.

Purpose

This study aimed to investigate whether Ang-(1-7) could reduce inflammation, improve bacterial clearance, and enhance survival in a murine model of pneumococcal pneumonia, alone or in combination with the antibiotic ceftriaxone.

Methods

A mouse model of S. pneumoniae pneumonia was used to evaluate the effects of Ang-(1-7). Mice received Ang-(1-7) treatment after infection, either alone or combined with ceftriaxone. Outcomes included leukocyte infiltration, pulmonary edema, lung tissue damage, cytokine production (TNF-α, IL-6, CXCL-1), bacterial load in bronchoalveolar lavage and blood, survival analysis, bone marrow-derived macrophage phagocytosis assays, and expression of lung barrier–associated genes.

Results

Ang-(1-7) reduced leukocyte infiltration, pulmonary edema, and lung tissue injury, and decreased pro-inflammatory cytokine levels. Treatment improved bacterial clearance in both lungs and bloodstream and increased survival in infected mice. Importantly, combining Ang-(1-7) with ceftriaxone further enhanced survival, even when treatment initiation was delayed. Mechanistically, Ang-(1-7) increased macrophage phagocytic activity and upregulated genes associated with lung barrier integrity.

Conclusion

Ang-(1-7) decreased inflammation, improved bacterial clearance, and enhanced survival in severe pneumococcal pneumonia. Its combination with ceftriaxone produced additive benefits, supporting Ang-(1-7) as a promising adjuvant therapeutic strategy in this infectious condition