Involvement of arachidonic acid metabolites in acute inflammation: detection of 6-keto-PGF1 alpha, thromboxane B2 and PGD2 in rat pleurisy induced by phorbol myristate acetate.

Rat pleurisy was induced by intrapleural injection of phorbol myristate acetate (PMA), a known tumor promotor and a component of croton oil. Pleural fluids at 30 min and 1 hr after PMA-injection were collected and arachidonic acid metabolites in the fluids were measured by RIA or bioassay after fractionation through reversed phase HPLC using an ODS column. The major metabolites found in the pleural fluid were 6-keto-PGF1 alpha, TXB2 and PGD2, with a small amount of PGE2. Pretreatment with 10 mg/kg indomethacin suppressed the pleural fluid accumulation and also reduced the amount of the above metabolites to the basal levels. Treatment with OKY-046, a novel thromboxane synthetase inhibitor, reduced the level of TXB2 completely, but had no effect on those of 6-keto-PGF1 alpha and PGD2, and it had no effect on pleural fluid accumulation either. The results may indicate that PGI2 plays a role for the vascular permeability increase in the early phase of pleurisy.