Vasculotide reduces pulmonary permeability in Streptococcus pneumonia infected and mechanically ventilated mice

Introduction Community acquired pneumonia (CAP), commonly caused by Streptococcus pneumonia (S.pn.), is a significant cause of mortality worldwide. Despite adequate antibiotic treatment, pneumococcal pneumonia is able to provoke pulmonary endothelial hyperpermeability leading to potentially lethal lung edema and acute-respiratory distress syndrome (ARDS). This condition often requires mechanical ventilation (MV) causing additional damage to the lung (Ventilator-induced lung injury; VILI). Angiopoietin-1 mediated Tie2-receptor activation stabilizes the endothelial barrier and reduces vascular hyperpermeability. The PEGylated (polyethylene glycol) Tie2-agonist Vasculotide (VT) mimics Angiopietin-1 effects. Moreover, we have recently shown that VT reduces pulmonary hyperpermeability in murine pneumococcal pneumonia. The aim of our study was to investigate whether VT could ameliorate lung injury in S.pn. infected and mechanically ventilated mice.

Methods Pulmonary hyperpermeability, immune cell response and bacterial load were quantified in S.pn. infected mice treated with Ampicillin ± VT before undergoing six hours of MV 24 h post infection. Additionally, histological analysis was performed to evaluate pathomorphological lung changes due to pneumonia and VILI.

Results Combination treatment with Ampicillin and VT significantly reduced pulmonary hyperpermeability, histological lung damage and edema formation in S.pn. infected and mechanically ventilated mice compared to mere antibiotic therapy. VT did not have any effect on local or systemic immune responses or bacterial burden.

Conclusion Our results suggest that adjunctive therapy with VT may reduce ventilator induced lung injury in severe pneumococcal pneumonia.