Abstract
BackgroundPulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure. In this study we determined whether treatment with TIP (AP301), a synthetic cyclic peptide that mimics the lectin-like domain of human TNF, decreases pulmonary edema in a mouse model of severe human RSV infection. TIP is currently undergoing clinical trials as a therapy for pulmonary permeability edema and has been shown to decrease pulmonary edema in different lung injury models.MethodsC57BL/6 mice were infected with pneumonia virus of mice (PVM) and received TIP or saline (control group) by intratracheal instillation on day five (early administration) or day seven (late administration) after infection. In a separate set of experiments the effect of multiple dose administration of TIP versus saline was tested. Pulmonary edema was determined by the lung wet-to-dry (W/D) weight ratio and was assessed at different time-points after the administration of TIP. Secondary outcomes included clinical scores and lung cellular response.ResultsTIP did not have an effect on pulmonary edema in different dose regimens at different time points during PVM infection. In addition, TIP administration did not affect clinical severity scores or lung cellular response.ConclusionIn this murine model of severe RSV infection TIP did not affect pulmonary edema nor course of disease.
Highlights
Pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure
Several studies of mice infected with the pneumovirus pneumonia virus of mice (PVM), which is frequently used as a model for severe human RSV have shown that alveolar edema was present in lung tissue [4,5]
Clinical response and pulmonary edema development during pneumovirus infection The first clinical signs of PVM disease in C57 mice appeared on day 6 after PVM infection and consisted of mild weight loss
Summary
Pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure. Several studies of mice infected with the pneumovirus pneumonia virus of mice (PVM), which is frequently used as a model for severe human RSV have shown that alveolar edema was present in lung tissue [4,5]. Based on these studies mechanical obstruction of the small airways and alveoli by edema appears to play a significant role in RSV-induced respiratory failure. Clinical studies on the consequences of pulmonary edema in RSV disease are lacking pulmonary edema is associated with prolonged respiratory failure and a higher mortality in other pulmonary conditions such as acute respiratory distress syndrome (ARDS) [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
