Modification by steroids of pulmonary oedema and prostaglandin E2 pharmacokinetics induced by endotoxin in rats.
1. A single i.p. injection of bacterial endotoxin in rats (3.5 mg kg-1) caused lung injury assessed as changes in lung dry:wet weight ratio and leukopaenia over the subsequent 28 h. 2. This treatment also slowed the efflux of 14C from [14C]-prostaglandin E2 (PGE2), i.e., increased t1/2 and increased the survival of PGE2 in isolated perfused lungs over the same period. 3. These effects of endotoxin were reversed by methylprednisolone (30 mg kg-1), given 30 min after the endotoxin. 4. Another synthetic corticosteroid, budesonide (1.2 mg kg-1) given 1 h before endotoxin partially prevented the lung injury and leukopaenia but did not affect the increased t1/2 for PGE2 nor its survival. 5. The reversal by methylprednisolone of both the physical signs of lung injury and the changes in PGE2 pharmacokinetics caused by endotoxin suggests that changes in PGE2 pharmacokinetics could serve as an index of acute lung injury following sepsis.
Izumi
T
T
Department of Pharmacology, Hunterian Institute, Royal College of Surgeons, London.
Bakhle
Y S
YS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019819:Budesonide; D015232:Dinoprostone; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology; D011458:Prostaglandins E / Q000493:pharmacokinetics*; D011654:Pulmonary Edema / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D011282:Pregnenediones; D011458:Prostaglandins E; D013256:Steroids; D019819:Budesonide; D015232:Dinoprostone; D008775:Methylprednisolone