PT  - JOURNAL ARTICLE
AU  - L. Homer
AU  - E. Launay
AU  - N. Joram
AU  - C. Jacqueline
AU  - P.-H. Jarreau
AU  - J. Caillon
AU  - T. Moyon
AU  - B. Branger
AU  - G. Potel
AU  - J. C. Roze
AU  - C. Méhats
AU  - C. Gras-LeGuen
TI  - Antenatal Phosphodiesterase 4 Inhibition Restores Postnatal Growth and Pulmonary Development in a Model of Chorioamnionitis in Rabbits
AID  - 10.1124/jpet.111.179085
DP  - 2012 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 620--628
VI  - 340
IP  - 3
4099  - http://jpet.aspetjournals.org/content/340/3/620.short
4100  - http://jpet.aspetjournals.org/content/340/3/620.full
SO  - J Pharmacol Exp Ther2012 Mar 01; 340
AB  - Chorioamnionitis is implicated in the pathophysiology of bronchopulmonary disease, and the associated inflammatory response is responsible for adverse effects on alveolar development. The aim of this work was to analyze the effects of a phosphodiesterase 4 (PDE4)-selective inhibitor, rolipram (a modulator of the inflammatory response), in an experimental model of chorioamnionitis on pulmonary development and on the processes of infection and inflammation. Rabbit mothers were assigned to four groups: 1) saline serum inoculation (controls); 2) Escherichia coli intrauterine inoculation (C+); 3) rolipram infusion (R+); and 4) E. coli inoculation + rolipram infusion (C+R+). High rates of morbility and mortality were noticed in mothers and pups (5 of 13 pregnant rabbits in groups with rolipram). Alveolar development, inflammation, and infection were analyzed in pups at day 0 and day 5. At day 0, in the context of chorioamnionitis, rolipram significantly decreased birth weight (p < 0.01) relative to that of controls (p < 0.05). At day 5, weight normalized in group C+R+ but not in group C+ relative to controls (p < 0.001); moreover, alveolar airspace volume was preserved in group C+R+ but not in group C+ (p < 0.05). Interstitial volume decreased in group C+ versus controls (p < 0.05) but was preserved in group C+R+. Specific alveolar area was not significantly modified by rolipram. No significant difference was found concerning bronchoalveolar lavage cellularity, and all blood cultures remained sterile. In this model of impaired alveologenesis, rolipram significantly preserved specific alveolar density. However, PDE4 inhibition induced antenatal fetal demise and growth retardation.