Output of prostanoids from rat lung following endotoxin and its modification by methylprednisolone

Endotoxin given intraperitoneally to rats induced leucopenia and pulmonary oedema over 28 hr. The output of cyclo-oxygenase products PGE2, PGF2 alpha, TxB2, and 6-oxo-PGF1 alpha, from the perfused lungs isolated from these rats was measured using as substrate either exogenous arachidonate or endogenous arachidonate stimulated by the calcium ionophore A23187. From exogenous or endogenous arachidonate, the major effects of endotoxin were increased TxB2 and PGF2 alpha output and decreased 6-oxo-PGF1 alpha output. Treatment with methylprednisolone 30 min after endotoxin prevented the pulmonary oedema and leucopenia. The output of TxB2 and PGF2 alpha was unaltered, whereas that of 6-oxo-PGF1 alpha was increased. Our results do not support the suggestion that the beneficial effects of methylprednisolone in this model of acute lung injury are due to inhibition of prostanoid synthesis. Benefit may be better correlated with increased PGI2 formation.