Modification by steroids of pulmonary oedema and prostaglandin E₂ pharmacokinetics induced by endotoxin in rats

Abstract

1 A single i.p. injection of bacterial endotoxin in rats (3.5 mg kg ')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 t112 and increased the survival of PGE2 in isolated perfused lungs over the same period. 3 These effects of endotoxin were reversed by methylprednisolone (30mgkg 1), given 30min after the endotoxin. 4 Another synthetic corticosteroid, budesonide (1.2mg kg') given h before endotoxin partially prevented the lung injury and leukopaenia but did not affect the increased t,,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.

Cytokines and cytokine inducers stimulate prostaglandin E 2 entry into the brain

“…It has also been shown that a single bolus of PGE 2 perfused through isolated lungs results in the recovery of 15%, i.e. in the order of 85% of the PGE 2 is metabolized after a single pass through the lungs [17]. In the present study the amount recovered in CSF samples was up to 0.5% of that given systemically into the marginal ear vein.…”