Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity.
Pulmonary fibrosis results from excessive fibroblast proliferation and increased collagen deposition and occurs in chronic lung disease of prematurity (CLD). Platelet-derived growth factor (PDGF)-BB is mitogenic for fibroblasts and levels are increased in fibrotic lung disorders. Systemic dexamethasone (DEX) treatment improves pulmonary function and reduces inflammation in infants with or at risk of CLD. However, the effect of DEX treatment on fibroblast activity, PDGF-BB and collagen synthesis in the lungs of CLD patients is uncertain. Bronchoalveolar lavage (BAL) fluids, obtained from 15 infants at risk of CLD before and after DEX treatment, were analysed for fibroblast mitogenicity, PDGF-BB, N-terminal propeptide of collagen type III (PIIINP) and interleukin (IL)-1beta levels and inflammatory cell numbers. After DEX treatment, the mitogenic activity of BAL fluid for fibroblasts was not reduced but increased. The change in mitogenicity correlated with a change in BAL fluid PDGF-BB levels. Furthermore, BAL fluid-induced fibroblast proliferation was blocked using an inhibitor of the PDGF receptor. DEX treatment did not influence PIIINP levels, but reduced IL-1beta levels and inflammatory cell numbers in BAL fluid. This study suggests that dexamethasone treatment does not reduce fibroblast proliferation despite apparent downregulation of inflammation. The present findings do not support the use of dexamethasone for prevention of the fibrotic response in infants at risk of chronic lung disease of prematurity.
Dik
W A
WA
Dept of Immunology, Division of Neonatology, Erasmus Medical Centre, Rotterdam, the Netherlands. w.dik@erasmusmc.nl
Versnel
M A
MA
Naber
B A
BA
Janssen
D J
DJ
van Kaam
A H
AH
Zimmermann
L J I
LJ
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D003907:Dexamethasone / Q000627:therapeutic use*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000517:prevention & control*; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone