Ovariectomy-Induced Dry Skin Increases IL-31-Induced Scratching Behavior in Mice

抄録

Dry skin and type 2 cytokines, IL-4/IL-13 and IL-31, have been reported to be involved in pruritus in skin diseases such as atopic dermatitis. IL-31 directly induces pruritus, but IL-4/IL-13 themselves have little or no potential to induce pruritus, whereas IL-4/IL-13 potentiate nerve activation by subthreshold doses of pruritogens such as histamine and IL-31 in vitro, and are involved in alloknesis in dry skin mouse models induced by ovariectomy and artificial barrier disruption. In this study, we investigated whether ovariectomy-induced dry skin with permeability barrier dysfunction enhances IL-31-induced pruritus in mice. Levels of spontaneous scratching behavior were higher than in ovariectomized mice than in sham-operated mice probably due to barrier disruption that could be accelerated by hair shaving. Levels of scratching behavior induced by intradermal administration of IL-31, regardless of single or repeated administration, were increased in ovariectomized mice compared to in sham-operated mice. Pre-intradermal administration of neutralizing antibodies against IL-4/IL-13 did not attenuate the level of IL-31-induced scratching behavior in ovariectomized mice. Our results show that the dry skin induced by ovariectomy is an itchy condition prone to pruritus, and this is the first report showing that the dry skin enhances the potential of IL-31 to induce pruritus in vivo.