Involvement of leukotriene B4 in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions

To elucidate the mechanisms of severe itch in atopic dermatitis, we investigated the role of leukotriene B-4, a potent itch mediator, in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions. Topical application of the BLT leukotriene B-4 receptor antagonist ONO-4057 inhibited spontaneous itch-related behaviour. The concentration of leukotriene B-4 was significantly increased in the lesional skin. The expression levels of 5-lipoxygenase were also elevated in the lesional skin, yet present throughout the epidermis of both healthy and lesional skin. These results suggest a role for leukotriene B-4 in chronic dermatitis-related itch. Sphingosylphosphorylcholine (SPC) was increased in the epidermis of the lesional skin. Moreover, intradermal injection of SPC elicited itch-related behaviours in healthy mice. Because SPC induces itch-related responses through the production of leukotriene B-4 in keratinocytes (J Invest Dermatol, 129, 2009, 2854), these results suggest that an increase in SPC induces leukotriene B-4-mediated itching in chronic dermatitis. BLT1 receptor and 5-lipoxygenase in the skin may be effective pharmacological targets for the treatment of itch in atopic dermatitis.