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1 Acute inflammation was induced in rabbit skin by intradermal injection of arachidonic acid. 2 Inflammation was assessed by the local accumulation of intravenously-injected '25I-serum albumin (plasma extravasation) and histologically (polymorphonuclear leucocyte, PMNL infiltration).3 Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were extracted from skin and fractionated using C,8 mini-columns. They were quantitated by specific radioimmunoassays and authenticated by reversed-phase high performance liquid chromatography analysis. 4 Maximally elevated levels of LTB4 and PGE2 were detected in skin 5 min after arachidonic acid injection. At subsequent times the eicosanoid content of the skin decreased.5 The decrease in the eicosanoid content of the skin was due to rapid clearance (t, approximately 5 min) via the microvasculature and not a consequence of metabolism. 6 The concentration of LTB4 and PGE2 measured in inflamed skin was sufficient to account for the plasma extravasation and PMNL infiltration induced by arachidonic acid. The model therefore is useful for evaluating the anti-inflammatory efficacy of inhibitors of arachidonic acid metabolism including 5-lipoxygenase inhibitors. 7 The consequences of the rapid clearance of LTB4 from inflammatory sites are discussed with respect to its measurement in inflammatory disease and its role as an acute inflammatory mediator.

The inflammatory reaction induced by the intradermal injection of arachidonic acid into the rabbit dermis has been investigated. Plasma extravasation was measured by the leakage of 125I‐albumin into the tissues and polymorphonuclear leukocyte (PMNL) accumulation was assessed histologically. Arachidonic, 5,8,11,14,17‐eicosapentaenoic and 8,11,14‐eicosatrienoic acids, but not oleic, linoleic or linolenic acids, caused a concentration‐related plasma extravasation following their intra‐dermal injection. The plasma extravasation induced by arachidonic acid was dependent on PMNLs. PMNL infiltration and plasma extravasation into arachidonic acid‐injected skin sites was inhibited by the mixed cyclo‐oxygenase‐lipoxygenase inhibitor, BW755C. Arachidonic acid‐induced plasma extravasation was inhibited by cyclo‐oxygenase and 5‐lipoxygenase inhibitors but not by the Paf antagonist, kadsurenone. The inflammation induced by arachidonic acid in the rabbit dermis may be a useful model for evaluating 5‐lipoxygenase inhibitors which could be potentially useful anti‐inflammatory agents for the treatment of psoriasis and other inflammatory diseases.

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