Roles of T(H)1 and T(H)2 cytokines in a murine model of allergic dermatitis

Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expr ession of the cytokines IL-4, IL-5, and IFN-gamma. The role of these cytoki nes in the pathogenesis of AD is nor known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with o valbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-gamma cytokine genes to assess the role of these cytokines in this model. OVA-sensitized skin from IL-5(-/-) mice had no detectable eosinophils and e xhibited decreased epidermal and dermal thickening. Sensitized skin from IL -4(-/-) mice displayed normal thickening of the skin layers but had a drast ic reduction in eosinophils and a significant increase in infiltrating T ce lls. These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein -2 (MIP-2), MIP-1 beta, and RANTES. Sensitized skin from IFN-gamma(-/-) mic e was characterized by reduced dermal thickening. These results suggest that both the T(H)2 cytokines IL-4 and IL-5 and the T (H)1 cytokine IFN-gamma play important roles in the inflammation and hypert rophy of the skin in AD.