Antenatal dexamethasone suppresses tumor necrosis factor-alpha expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats

The hypoplastic lung in congenital diaphragmatic hernia (CDH) has both a qu antitative and qualitative reduction in surfactant. Tumor necrosis factor-a lpha (TNF-alpha) drastically decreases surfactant phospholipids synthesis b y isolated human type II pneumocytes. Recently, it was shown that TNF-alpha mRNA expression is increased in human hypoplastic CDH lung. Antenatal gluc ocorticoid therapy demonstrates improved surfactant biochemical immaturity in an animal CDH model. The aim of this study was to investigate the effect of antenatal dexamethasone (Dex) on TNF-alpha protein and gene expression in nitrofen-induced CDH hypoplastic lung in rats. A CDH model was induced i n pregnant rats after the administration of nitrofen on d 9.5 of gestation. Dex was given intraperitoneally on d 18.5 and 19.5. Cesarean section was p erformed on d 21. In situ hybridization was performed with a rat TNF-alpha- specific and digoxigenin-labeled oligonucleotide probe. TNF-alpha level was measured in solubilized lungs tissue extracts by ELISA. In control lung, T NF-alpha mRNA expression was weak or absent. In contrast, strong TNF-alpha mRNA expression was demonstrated in type II pneumocytes and bronchiolar epi thelium in CDH lung. In Dex-treated CDH lung, TNF-alpha mRNA expression was weak in both type II pneumocytes and the bronchiolar epithelium. The level of TNF-alpha was elevated significantly in CDH lung compared with levels i n control lung extracts (p < 0.01). In Dex-treated CDH lung, TNF-alpha prot ein was significantly decreased compared with CDH lung (p < 0.05). Our find ings suggest that the reduction in the local production of TNF-alpha may be one contributing mechanism by which antenatal glucocorticoid therapy impro ves pulmonary parenchymal immaturity, including surfactant.