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14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de
Introduction:
Community acquired pneumonia, commonly caused by Streptococcus pneumonia (S.pn.), is a significant cause of mortality worldwide. Despite adequate antibiotic treatment, pneumococcal pneumonia may provoke pulmonary endothelial hyperpermeability leading to acute-respiratory distress syndrome, which frequently requires mechanical ventilation (MV) causing additional damage to the lung (Ventilator-induced lung injury; VILI). Angiopoietin-1 mediated Tie2-receptor activation stabilizes lung endothelial barrier and reduces vascular permeability. We have recently shown that the PEGylated (polyethylene glycol) Angiopietin-1 mimic Vasculotide (VT) reduces lung 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 and undergoing six hours of MV 24h post infection. Histologic analysis was performed to evaluate pathomorphological lung changes due to pneumonia and VILI.
Results:
VT did not alter local or systemic immune responses or bacterial burden. Interestingly, 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.
Conclusion:
Our results suggest that adjunctive therapy with VT may reduce ventilator- induced lung injury in severe pneumococcal pneumonia.