Contact hypersensitivity (CHS) is characterized by the percutaneous penetration of a low molecular weight hapten and the cross-talk between lymphocytes and antigen-presenting cells. Following our investigations into the role of reactive nitrogen species (RNS) in this process, we have now studied the effect of three phenolics obtained from Phagnalon rupestre (Asteraceae) on CHS. The three compounds, which have previously been described as inhibitors of peroxynitrite reactivity, are 2-isoprenylhydroquinone-1-glucoside (IHG), 3,5-dicaffeoylquinic acid (DCA) and 3,5-dicaffeoylquinic acid methyl ester (DCE) [1]. The experimental design begins with the sensitization with oxazolone on abdominal mouse skin followed by the subsequent elicitation with the same agent on the ear five days later [2]. Inflammation end points include histological analyses and determination of the presence of cytokines, 3-nitrotyrosine and inducible NO synthase (iNOS). Dunnett's t values measures statistical significance.
The most active compound was DCE, which inhibited ear swelling by 54% 24h after the challenge with oxazolone. Its free acid form (DCA) produced a 40% inhibition. The levels of IL-1β were always parallel to the time course observed for swelling. IL-4 evolved similarly in a lower range. Both caffeoyl esters significantly affected the liberation of interleukins, with DCE reducing the IL-4 levels at both 24 and 96h by 78 and 87%, respectively. Of all the test compounds, only IGH was able to reduce iNOS expression. Taken together with our previous results, these findings suggest that the efficacy on CHS is associated with antioxidant potency rather than with the ability to inhibit RNS production.
Acknowledgements: Ana Olmos is recipient of a grant from Generalitat Valenciana. This work was supported by the Spanish Ministry of Science and Technology (SAF 2002–00723).
References: 1. Olmos, A. et al. (2005), Nitric Oxide 12: 54–60. 2. Wang, B. et al. (2000), J. Immunol. 165: 6783–6790.
