4.6 Article

Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury

期刊

EUROPEAN RESPIRATORY JOURNAL
卷 31, 期 3, 页码 633-644

出版社

EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00071307

关键词

bronchopulmonary dysplasia; coagulation; fibrin deposition; oxidative stress; piclamilast; rolipram

资金

  1. NHLBI NIH HHS [R01 HL055534, R01 HL092158, HL-55534] Funding Source: Medline

向作者/读者索取更多资源

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.

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