A new assay for antiphlogistic activity: zymosan-induced mouse ear inflammation.

A new model of local inflammation has been developed: intradermal zymosan-induced mouse ear edema. The symptoms of inflammation induced by injecting zymosan into one of the ears were followed up for 72 h. The ear edema and the local accumulation of polymorphonuclear leukocytes' (PMN) marker enzyme, myeloperoxidase (MPO), were determined. Edema peaked at 4-6 h, while MPO activity peaked at 24 h after zymosan application. The correlation between inflammatory response and concentration of zymosan was also tested. Of the various concentrations tested, 1% suspension has been found optimal. Anti-inflammatory drugs and mediator antagonists were examined in order to establish the selectivity and sensitivity of the assay. A glucocorticoid (dexamethasone), two cyclooxygenase inhibitors (indomethacin, piroxicam) and an interleukin-1 (IL-1) release inhibitor (IX 207-887, Sandoz) all reduced edema and MPO activity as well. However, a lipoxygenase inhibitor (phenidone), a serotonin receptor antagonist (methysergide) and H1 and H2 receptor antagonists (clemastine and cimetidine, respectively) all failed to inhibit the reaction.