ARACHIDONIC-ACID (AA) AND TETRADECANOYLPHORBOL ACETATE (TPA) EXERT SYSTEMIC EFFECTS WHEN APPLIED TOPICALLY IN THE MOUSE

We studied the systemic actions of topically applied arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) in the mouse. AA or TPA-in duced ear edema, increases in vascular permeability, eicosanoid levels , neutrophil and mononuclear influx were determined in both phlogogen- treated and contralateral vehicle-treated ear of each mouse and were c ompared with vehicle-treated ears from control mice. Edema and vascula r permeability increases appeared only in AA- or TPA-applied ears. Mor eover, in contralateral ears from AA-treated mice an increase in 6-ket o-PGF(1 alpha) and LTB4 was found. Only LTB4 increased in the contrala teral ear after TPA. Contralateral ears from AA- or TPA-treated mice a lso showed a significant increase in MPO levels. The increased levels of 6-keto-PGF(1 alpha) but not those of LTB4 in contralateral ears wer e reduced by indomethacin applied simultaneously with the phlogogen. A A also increased plasma and serum levels of LTB4, but not those of 6-k eto-PGF(1 alpha). In contrast, TPA increased plasma and serum levels o f 6-keto-PGF(1 alpha) and LTB4. The results show that both AA and TPA applied topically exert systemic effects.