Possible Involvement of Type 2 Cytokines in Alloknesis in Mouse Models of Menopause and Dry Skin

Alloknesis, an abnormal itch sensation induced by innocuous stimuli, is a key phenomenon in the vicious itch-scratch cycle in patients with atopic dermatitis. Dry skin and pruritus, including alloknesis, are major health problems in peri- and post-menopausal women. We recently reported permeability barrier dysfunction in ovariectomized (OVX) mice-a model of menopause-and found that the dysfunction was related to dry skin. However, the mechanism of the itch remains unknown. Therefore, we examined touch- and pruritogen-evoked alloknesis and epidermal innervation in OVX mice and acetone, diethyl ether and water (AEW)-treated mice, for the experimental dry skin model. Both alloknesis and epidermal innervation were comparable in OVX and AEW mice. Neutralizing antibodies against IL-4 and IL-13 inhibited alloknesis in both OVX and AEW mice as early as 30 min after intradermal administration. Comparable values close to the measurement limit of IL-4 were found in the skin of HRT and Sham mice as well as AEW and the control mice, but the levels of IL-4 were within the measurement limit in OVX mice. We could not detect mRNAs of IL-4 or IL-13 in any groups of mice. On the other hand, the number of eosinophils and basophils was increased in OVX and AEW mice. These results suggest that impaired barrier function in cooperation with type 2 cytokines derived from eosinophils and basophils in the skin or with endogenous type 2 cytokine may trigger the development of alloknesis, and thus, these cytokines could be a therapeutic target for sensitive skin.