Changes in adrenomedullin in bronchoalveolar lavage fluid with chorioamnionitis in a sheep-based model

Background: Adrenomedullin (AM) is a potent angiogenic, antioxidant and anti-inflammatory peptide protecting the developing lung from injury due to bronchopulmonary dysplasia (BPD) of the preterm infant. At this stage, no data on the potential effects of chorioamnionitis (CA) occurrence and glucocorticoids (GC) administration on AM in developing lungs are still lacking. Objective: to investigate, in a sheep-based model, the positive/side-effects of combined exposure to CA and GC on AM concentrations measured in bronchoalveolar lavage fluid (BALF). Methods: Time-mated ewes were randomly admitted to one of six treatment groups receiving injection: saline (controls); lipopolysaccharide (L) in intra-amniotic fluid treated alone at 7 or 14 d before delivery or associated with betamethasone (B) intramuscularly; B treated alone (7d) or associated with L (14d). Lambs were surgically delivered at 120 days gestation and euthanized. BALF was used for AM measurement in the studied groups. Results: AM BALF levels significantly (p < 0.05, for all) changed both to B and L exposure in a time-dependent manner. The latter was characterized by AM levels at short term superimposable to controls, whilst significantly (p > 0.05) decreased at long-term. The former showed increased AM at short and decreased at long-term (p < 0.05, for all), respectively. Conclusions: the present results showing AM BALF changes in a sheep-based model support the AM role in the hemodynamic patterns due to CA and BPD occurrence and open the way to further studies investigating the role of vasoactive agents as trustable markers of lung development/damage.