ABSTRACT
BACKGROUND AND PURPOSE: The phenolic compounds isoprenylhydroquinone glucoside (IHG), 3,5-dicaffeoylquinic acid (DCA), and its methyl ester (DCE) have previously been shown to inhibit both contact hypersensitivity (CHS) and peroxynitrite reactivity. The present work seeks to establish a relationship between the anti-inflammatory effect and the release of cytokines and tyrosine nitration in skin. EXPERIMENTAL APPROACH: Murine CHS was developed by means of sensitization and challenge with dinitrofluorobenzene (DNFB) or oxazolone. Ear swelling was measured 24 and 96 h after challenge. Interleukin (IL)-1beta, IL-4, and tumour necrosis factor (TNF)-alpha were measured by ELISA; and the expression of inducible nitric oxide synthase (iNOS) was detected by Western blotting. Histological samples were analysed for 3-nitrotyrosine. KEY RESULTS: In the oxazolone model, DCE reduced the 24 h swelling by 54% whereas the effect of DCA was lower (40% inhibition). All the test compounds reduced IL-1beta values 24 h after challenge with DNFB or oxazolone, DCE particularly inhibited IL-4 production (74% and 78%, respectively; P<0.01). Tyrosine nitration was also markedly reduced by DCE. In general, the test compounds limited the presence of polymorphonuclear (PMN) leukocytes in the skin. CONCLUSIONS AND IMPLICATIONS: These results suggest that the effect of 3,5-dicaffeoylquinic esters on CHS is associated with a decrease in the production of interleukins, but not with the inhibition of iNOS expression. Moreover, esterification of the carboxyl group at C-1 enhanced protection against tyrosine nitration in the skin.