Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats.
BACKGROUND
Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of corticosteroid treatment starting before or at the time of lung injury. However, this is not representative of the human condition as treatment only begins after disease has been established. We examined the effect of a short course corticosteroid treatment starting 3 days after bleomycin induced lung injury on the development of pulmonary fibrosis.


METHODS
Bleomycin (1.5 mg/kg) was instilled intratracheally into rats to induce pulmonary fibrosis. The effect of a 3-day course of dexamethasone (0.5 mg/kg) initiated 3 days after bleomycin induced lung injury on cell proliferation and collagen deposition was examined by analysing bronchoalveolar lavage (BAL) fluid and lung tissue.


RESULTS
Treating bleomycin exposed animals after injury with dexamethasone for 3 days inhibited lung collagen deposition compared with animals exposed to bleomycin without dexamethasone treatment (15.2 (2.2) mg collagen/lung v 22.5 (2.1) mg/lung; p<0.05). Dexamethasone treatment reduced pulmonary parenchymal cell proliferation in bleomycin exposed rats but did not influence BAL fluid mitogenic activity for lung fibroblasts or alter the BAL fluid levels of the fibrogenic mediators transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin.


CONCLUSIONS
A 3 day course of dexamethasone treatment initiated 3 days after bleomycin induced lung injury reduces lung cell proliferation and collagen deposition by mechanisms other than through reduction of transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin levels in BAL fluid. We propose that an early short course treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis.
Dik
W A
WA
Department of Immunology, Division of Neonatology, Erasmus MC, University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. w.dik@erasmusmc.nl
McAnulty
R J
RJ
Versnel
M A
MA
Naber
B A E
BA
Zimmermann
L J I
LJ
Laurent
G J
GJ
Mutsaers
S E
SE
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003094:Collagen / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage*; D005347:Fibroblasts; D005938:Glucocorticoids / Q000008:administration & dosage*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011917:Rats, Inbred Lew
D000903:Antibiotics, Antineoplastic; D005938:Glucocorticoids; D001761:Bleomycin; D003907:Dexamethasone; D003094:Collagen