Roles of TH 1 and TH 2 cytokines in a murine model of allergic dermatitis


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Abstract

Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-[small gamma, Greek]. The role of these cytokines in the pathogenesis of AD is not known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-[small gamma, Greek] cytokine genes to assess the role of these cytokines in this model.OVA-sensitized skin from IL-5-/- mice had no detectable eosinophils and exhibited decreased epidermal and dermal thickening. Sensitized skin from IL-4-/- mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells. 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[small beta, Greek], and RANTES. Sensitized skin from IFN-[small gamma, Greek]-/- mice was characterized by reduced dermal thickening.These results suggest that both the TH 2 cytokines IL-4 and IL-5 and the TH 1 cytokine IFN-[small gamma, Greek] play important roles in the inflammation and hypertrophy of the skin in AD.J.Clin. Invest. 103:1103-1111 (1999).

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