title: Glucocorticoids and erythropoietin in chronic lung disease of prematurity: Proliferative potential in lung fibroblast and epithelial cells exposed to tracheal aspirates.
abstract: BACKGROUND
  We investigated the effects of glucocorticoids, erythropoietin (EPO) and spironolactone (SPL) n human fetal lung fibroblasts and human alveolar epithelial cells exposed to tracheal aspirate fluid (TAF) from extremely premature infants with chronic lung disease (CLD), characterized by fibrosis and changes in the alveolar epithelium.
  
  
  METHODS
  Fibroblasts and epithelial cells (FHs 738Lu and A549, respectively) were treated with different concentrations of hydrocortisone (HDC), dexamethasone (DEX), betamethasone (BET), SPL, and EPO in the absence or presence of TAF from infants with CLD (gestational age, 25.3 ± 0.8 weeks; birthweight, 658 ± 77 g; postnatal age, 0-28 days) and assayed for proliferation.
  
  
  RESULTS
  Exposure to TAF resulted in a concentration-dependent proliferation of fibroblasts and epithelial cells. Proliferation of TAF-exposed fibroblasts was suppressed most significantly by 100 μmol/L DEX (21%, P = 0.046) and 300 mIU/mL EPO (18%, P = 0.02) and promoted most significantly by 0.4 μmol/L HDC (10%, P = 0.04). Epithelial proliferation was promoted by 4 μmol/L HDC (15%, P = 0.04), 10 μmol/L DEX (53%, P < 0.01), 0.2 μmol/L BET (56%, P < 0.01), and 300 mIU/mL EPO (35%, P < 0.01) in the presence of TAF. Treatment with glucocorticoids alone did not significantly affect fibroblast proliferation.
  
  
  CONCLUSIONS
  Glucocorticoids and EPO reduced fibroproliferation while promoting epithelial cell growth in vitro within certain dose ranges. Appropriate doses of glucocorticoids and EPO may be useful in the prevention and resolution of CLD in extremely premature infants.
authors.affiliation: Department of Pediatrics Osaka City University Graduate School of Medicine, Osaka, Japan.|Department of Neonatology Osaka City General Hospital, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohnishi
authors.affiliation: Department of Neonatology Osaka City General Hospital, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ichiba
authors.affiliation: Department of Pediatrics Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Pediatrics Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamazaki
authors.affiliation: Department of Pediatrics Osaka City University Graduate School of Medicine, Osaka, Japan.|Department of Neonatology Osaka City General Hospital, Osaka, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumura
authors.affiliation: Department of Pediatrics Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005865:Gestational Age; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000473:pathology; D008171:Lung Diseases; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology*; D014132:Trachea / Q000187:drug effects / Q000473:pathology*
chemical_list: D005938:Glucocorticoids; D004921:Erythropoietin
keywords: chronic lung disease; erythropoietin; glucocorticoids; premature infant; tracheal aspirate fluid