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

Pneumonia caused by Streptococcus pneumoniae remains a major health issue with significant morbidity and mortality. This study investigates the therapeutic potential of Angiotensin-(1–7) [Ang-(1–7)], a peptide with anti-inflammatory and pro-resolving effects, in a murine model of pneumococcal pneumonia. In mice infected with S. pneumoniae , Ang-(1–7) reduced leukocyte infiltration, pulmonary edema, and tissue damage, and lowed production of the pro-inflammatory cytokines TNF-α, IL-6, and CXCL-1. The treatment improved bacterial clearance in the bronchoalveolar lavage and blood and increased survival rates. Importantly, when combined with the antibiotic ceftriaxone, Ang-(1–7) enhanced survival even when treatment started late in this model of pneumococcal pneumonia. Mechanistically, Ang-(1–7) enhanced the phagocytic activity of S. pneumoniae by bone marrow-derived macrophages and increased the expression of genes associated with lung barrier integrity. These results show that treatment with Ang-(1–7) decreases inflammation and improves outcomes in severe and invasive pneumococcal pneumonia, especially when combined with antibiotics, suggesting it may be a useful adjuvant therapeutic strategy in this infectious condition.