Related Experiment Video
Updated: Jul 9, 2026

Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury
Y P de Visser1, F J Walther, E H Laghmani
1Dept of Pediatrics, Division of Neonatology, P3-P30, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Insights
Phosphodiesterase-4 (PDE4) inhibitors, like piclamilast, improved survival in pre-term rat pups with lung injury. PDE4 inhibition reduced inflammation and fibrin deposition, suggesting therapeutic potential for bronchopulmonary dysplasia.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Neonatology
Background:
- Phosphodiesterase-4 (PDE4) inhibitors are explored for respiratory diseases like asthma and COPD.
- Bronchopulmonary dysplasia (BPD) is a significant concern in premature infants, necessitating novel therapeutic strategies.
- Selective PDE4 inhibitors may offer a therapeutic option for BPD.
Purpose of the Study:
- To investigate the anti-inflammatory effects of two PDE4 inhibitors, rolipram and piclamilast, in a pre-term rat model of hyperoxia-induced lung injury.
- To assess the impact of prolonged PDE4 inhibitor therapy on survival, lung pathology, and key gene expression in experimental BPD.
Main Methods:
- Pre-term rat pups were exposed to room air, hyperoxia, or hyperoxia plus rolipram or piclamilast.
- Evaluated survival, histopathology, fibrin deposition, alveolar vascular leakage, and differential mRNA expression (real-time RT-PCR) of genes related to inflammation, coagulation, and fibrinolysis.
Main Results:
- PDE4 inhibitor therapy extended median survival by up to 7 days.
- Reduced alveolar fibrin deposition, lung inflammation, and vascular leakage.
- Decreased monocyte/macrophage influx and protein efflux in bronchoalveolar lavage fluid.
- Significant improvement in mRNA expression of genes involved in inflammation, fibrin deposition, and alveolarization.
Conclusions:
- Phosphodiesterase-4 inhibition prolongs survival in pre-term rat pups with neonatal hyperoxic lung injury.
- PDE4 inhibition effectively reduces inflammation and alveolar fibrin deposition.
- Piclamilast demonstrated superior efficacy compared to rolipram in this model.
Abstract:
Phosphodiesterase-4 (PDE4) inhibitors may offer novel therapeutic strategies in respiratory diseases, including asthma and chronic obstructive pulmonary disease. Therefore, selective PDE4 inhibitors may also provide a therapeutic option for very pre-term infants with bronchopulmonary dysplasia (BPD). The anti-inflammatory effect of two PDE4 inhibitors was investigated in a pre-term rat model of hyperoxia-induced lung injury. Pre-term rat pups were exposed to room air, hyperoxia, or hyperoxia and one of two PDE4 inhibitors: rolipram and piclamilast. The anti-inflammatory effects of prolonged PDE4 inhibitor therapy were investigated by studying survival, histopathology, fibrin deposition, alveolar vascular leakage and differential mRNA expression (real-time RT-PCR) of key genes involved in inflammation, alveolar enlargement, coagulation and fibrinolysis. PDE4 inhibitor therapy prolonged median survival by up to 7 days and reduced alveolar fibrin deposition, lung inflammation and vascular leakage by decreasing the influx of monocytes and macrophages and protein efflux in bronchoalveolar lavage fluid. Analysis of mRNA expression of key genes involved in experimental BPD revealed a significant PDE4 inhibitor-induced improvement of genes involved in inflammation, fibrin deposition and alveolarisation. In conclusion, phosphodiesterase-4 inhibition prolongs survival by inhibiting inflammation and reducing alveolar fibrin deposition in pre-term rat pups with neonatal hyperoxic lung injury, whereby piclamilast outperformed rolipram.
Related Concept Videos
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Pneumonia IV: Management
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:

