Inhibition of Irritation and Contact Hypersensitivity by Ethacrynic Acid

Abstract

The immunosuppressive effect of topical ethacrynic acid (ECA) was tested on both the induction and elicitation phases of contact sensitization in a mouse model. ECA (0.5% in vehicle) reduced the sensitization response by >50% when the sensitizer was either dinitrochlorobenzene (DNCB), oxazalone (OX) or para-phenylenediamine (PPD), and was applied 1 day later to the ECA-pretreated skin site. The immunosuppressive effect of combining ECA with either hydrocortisone or with cis-urocanic acid was also tested. An additive suppressive effect was observed with ECA in both combinations. The effect of ECA (1% in vehicle) on blocking the elicitation phase was also examined in a mouse ear edema assay. ECA was highly effective in preventing the challenge response in mice previously sensitized to either DNCB, OX or PPD. ECA (1% in vehicle) was also tested for its ability to inhibit contact irritation. ECA (1% in vehicle) was highly effective in preventing ear edema due to topically applied skin irritants including arachidonic acid, capsaicin, lactic acid, phorbol myristate acetate, trans-retinoic acid, and sodium lauryl sulfate. ECA may be useful for both prophylaxis and therapeutic treatment of diverse skin conditions including contact dermatitis, eczema, and other related allergic skin disorders.