PHARMACOLOGICAL MODULATION OF PICRYL CHLORIDE-INDUCED CONTACT-DERMATITIS IN THE MOUSE

A biphasic response of ear swelling was observed 2 h and 24 h after application of the antigen to picryl chloride-sensitized Balb/c mice. A platelet-activating factor (PAF) antagonist, BN 52063, or the anti-inflammatory drug, betamethasone, applied topically or injected subcutaneously, inhibited in a dose-dependent fashion the antigen-induced increase in ear thickness observed after 24 h. In addition, BN 52063 and betamethasone presented a synergistic effect when administered in vivo simultaneously and subcutaneously. Indomethacin administered subcutaneously at the time of the antigen challenge significantly potentiated the early swelling phase and inhibited the late one. In contrast, the inhibitors of histamine and serotonin, ketotifen and methysergide, respectively, modulated mostly the early, and to a lower extent the late phase when administered at the time of antigen challenge. In contrast, none of these drugs inhibited the late phase reaction when administered 4 h after the antigen. A significant eosinophil and mononuclear-cell ear infiltrate was observed following topical application of the antigen, a phenomenon that was markedly reduced by either BN 52063 or betamethasone. These results demonstrate the effectiveness of PAF antagonists, either alone or in association with glucocorticosteroids, in experimental CD, the modulation of the infiltration of eosinophils and mononuclear cells possibly explaining part of the inhibitory action of these drugs.