Effect of prostaglandin E1 infusion on leukocyte traffic and fibrosis in acute lung injury induced by bleomycin in hamsters.
OBJECTIVE
To determine whether the iv infusion of prostaglandin E1 (PGE1) could modify the early influx of neutrophils into bleomycin-injured lungs and if that would affect subsequent development of inflammation and fibrosis.


METHODS
In vivo controlled animal study performed in a university hospital pulmonary research laboratory. Male Syrian golden hamsters (100- to 110-g body weight) were divided into four treatment groups: a) No treatment; b) intratracheal bleomycin plus PGE1 infusion; c) bleomycin plus saline infusion; d) PGE1 infusion only. PGE1 (180 ng/hr.100 g) or saline were infused iv 3 to 25 hr after intratracheal instillation of bleomycin sulfate (0.5 U/0.5 mL.100 g). Total and differential counts of cells recovered by lavage, lavage fluid protein, and lung total protein and hydroxyproline levels were measured from 6 hr to 30 days later.


RESULTS
PGE1 infusion reduced the influx of neutrophils 6 hr after bleomycin injury by 53% compared with saline infusion (p less than .0001), but increased inflammatory cell traffic after 24 hr for 15 days. At 4 days, protein recovered in lung lavage fluid was also decreased in PGE1-treated, bleomycin-injured animals, reflecting reduced injury to lung permeability barriers. Accumulation of lung collagen in the PGE1-treated, bleomycin-instilled hamsters tended to be lower than in the bleomycin-injured, saline-infused group at 15 and 30 days, although these differences did not achieve statistical significance. Despite this fact, greater than 33% of the animals in the PGE1-treated group died, possibly indicating an increased risk of sepsis in these animals.


CONCLUSIONS
PGE1 infusion can decrease early neutrophil traffic and reduce injury to the lung permeability barriers. However, this treatment augments late inflammatory events and does not significantly alter the development of fibrosis.
Grant
M M
MM
Division of Pulmonary and Critical Care Medicine, Winthrop-University Hospital, Mineola, NY 11501.
Burnett
C M
CM
Fein
A M
AM
D000208:Acute Disease; D000527:Alprostadil / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D006909:Hydroxyproline / Q000032:analysis; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D011506:Proteins / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology
D011506:Proteins; D001761:Bleomycin; D000527:Alprostadil; D006909:Hydroxyproline