Arachidonic acid (AA) injected into hindpaws of Lewis rats produces a severe edematous response. Treatment with corticosteroids (dexamethasone, prednisolone), dual inhibitors of arachidonate metabolism (phenidone, SK & F 86002), anti-histamine/serotonin agents (chlorpheniramine, cyproheptadine) and a gold compound (auranofin) inhibited AA-induced edema. In contrast, administration of high doses of cyclooxygenase inhibitors (indomethacin, piroxicam, naproxen, ibuprofen, meclofenamic acid and tiflamizole) did not affect AA-induced hind paw edema. The involvement of lipoxygenase products and mast cell mediators in the edematous response to arachidonic acid render this model potentially useful for studying antiinflammatory agents with a mechanism of action different from that of cyclooxygenase inhibitors.

Arachidonic Acid (AA) injected into a hindpaw of Lewis rats produces high levels of tissue myeloperoxidase (MPO), a biochemical marker for PMN leukocytes. Treatment with a corticosteroid (prednisolone) or dual 5-LO/CO inhibitors of AA metabolism (phenidone, SKF 86002) produced dose-related inhibition of AA-induced elevations in paw tissue MPO levels. In contrast, administration of high pharmacologic doses of selective cyclooxygenase inhibitors (indomethacin, ibuprofen, naproxen), anti-histamine/serotonin agents (cyproheptadine, chlorpheniramine) or an anti-arthritic gold compound (auranofin) produced only slight or moderate effects. Thus, AA-induced hindpaw inflammation is a useful method for determining pharmacologic effects of 5-LO/CO inhibitors on PMN leukocyte infiltration in vivo.

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