The effect of TIP on pneumovirus-induced pulmonary edema in mice
Elske van den Berg1, Reinout A Bem1, Albert P Bos1
1Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Background:
Pulmonary 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.
Methods:
C57BL/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.
Results:
TIP 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.
Conclusion:
In this murine model of severe RSV infection TIP did not affect pulmonary edema nor course of disease.
Insights
Treatment with TIP (AP301) did not reduce pulmonary edema or disease severity in a mouse model of severe respiratory syncytial virus (RSV) infection. Further research is needed to explore TIP
Area of Science:
- Pulmonary medicine
- Virology
- Pharmacology
Background:
- Pulmonary edema is a key factor in respiratory syncytial virus (RSV)-induced respiratory failure.
- TIP (AP301), a synthetic peptide, is being investigated for pulmonary permeability edema.
- Previous studies suggested TIP reduces edema in lung injury models.
Purpose of the Study:
- To evaluate TIP's efficacy in reducing pulmonary edema in a severe RSV mouse model.
- To assess TIP's impact on clinical scores and lung cellular response.
Main Methods:
- C57BL/6 mice were infected with pneumonia virus of mice (PVM).
- TIP or saline was administered intratracheally at early or late stages post-infection.
- Pulmonary edema was measured by lung wet-to-dry weight ratio.
Main Results:
- TIP administration did not significantly affect pulmonary edema at various doses or time points.
- Clinical severity scores and lung cellular responses remained unchanged with TIP treatment.
Conclusions:
- TIP did not demonstrate efficacy in mitigating pulmonary edema or disease progression in this PVM infection model.
- The findings do not support TIP as a treatment for RSV-induced pulmonary edema in this model.
