Inositol–Trisphosphate Reduces Alveolar Apoptosis and Pulmonary Edema in Neonatal Lung Injury

• DOI: 10.1165/rcmb.2011-0262oc
• Publication Date: 2012-03-09T05:20:46Z
• Authors: Stefanie Preuß; Sabrina Stadelmann; Friede D. Omam; Julia Scheiermann; Supandi Winoto-Mo...; Philipp von Bismarck; Friederike Knerli...; Dennis Lex; Sabine Adam-Klages; Daniela Wesch; Janka Held-Feindt; Stefan Uhlig; Stefan Schütze; Martin F. Krause
• Keywords: Male; 0301 basic medicine; Caspase 8; Interleukin-6; Pulmonary Gas Exchange; Inositol Phosphates; Acute Lung Injury; Apoptosis; Pulmonary Edema; Ceramides; Amphiregulin; 3. Good health; Pulmonary Alveoli; Disease Models, Animal; 03 medical and health sciences; Animals, Newborn; Animals; Intercellular Signaling Peptides and Proteins; Female; Bronchoalveolar Lavage Fluid; Lung; Lymphotoxin-alpha; Glycoproteins

D-myo-inositol-1,2,6-trisphosphate (IP3) is an isomer of the naturally occurring second messenger D-myo-inositol-1,4,5-trisphosphate, and exerts anti-inflammatory antiedematous effects in lung. Myo-inositol (Inos) a component IP3, thought to play important role prevention neonatal pulmonary diseases such as bronchopulmonary dysplasia acute lung injury (nALI). Inflammatory are characterized by augmented acid sphingomyelinase (aSMase) activity leading ceramide production, pathway that promotes increased vascular permeability, apoptosis, surfactant alterations. A novel, clinically relevant triple-hit model nALI was developed, consisting repeated airway lavage, injurious ventilation, lipopolysaccharide instillation into airways, every 24 hours. Thirty-five piglets were randomized one four treatment protocols: control (no intervention), alone, + Inos, IP3. After 72 hours mechanical lungs excised from thorax for subsequent analyses. Clinically, oxygenation ventilation improved, extravascular water decreased significantly with S IP3 intervention. In tissue, we observed aSMase concentrations, caspase-8 reduced alveolar epithelial expression interleukin-6, transforming growth factor-β1, amphiregulin (an factor), migration blood-borne cells particularly CD14(+)/18(+) (macrophages) airspaces, lower surface tensions IP3-treated but not Inos-treated piglets. We conclude admixture surfactant, improves gas exchange edema our suppression governing enzyme aSMase, this deserves clinical evaluation.