Effect of retinoids on dermal inflammation and on arachidonic acid mobilization and metabolism in murine 3T6 fibroblasts retinoids, arachidonate release and metabolism.

Retinoids have shown anti-inflammatory activity in some animal models and human diseases, although the mechanism by which retinoids elicit this activity is unknown. In this study, retinoids significantly attenuated, in a dose-dependent fashion, murine ear oedema induced by phorbol 12-myristate 13-acetate (PMA) or oxazolone. Dexamethasone inhibited both oedemas whereas ketoprofen reduced only that induced by PMA. PMA application or oxazolone-induced contact hypersensitivity markedly increased production of eicosanoids such as 6-keto-PGF1 alpha or LTB4. The anti-oedematous effects of retinoids were accompanied by inhibition of tissue eicosanoid levels. Besides, retinoids showed toxic effects on culture fibroblasts caused by an irritant effect on plasma membrane. However, when we used subtoxic doses, we demonstrated that retinoids in vitro could inhibited arachidonate mobilization and eicosanoid biosynthesis induced in fibroblast cultures by PMA, calcium ionophore A23187 or bradykinin. Thus, this paper reports the ability of retinoids to inhibit skin inflammatory processes induced by tumour promotors or immunological stimuli. Moreover, we have demonstrated that retinoids at non-cytotoxic doses may inhibit eicosanoid generation and arachidonic acid mobilization in 3T6 fibroblasts.