Roles of TH1 and TH2 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 expression of the cytokines IL-4, IL-5, and IFN-gamma. 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-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 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-1beta, and RANTES. Sensitized skin from IFN-gamma-/- mice was characterized by reduced dermal thickening. These results suggest that both the TH2 cytokines IL-4 and IL-5 and the TH1 cytokine IFN-gamma play important roles in the inflammation and hypertrophy of the skin in AD.
Spergel
J M
JM
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mizoguchi
E
E
Oettgen
H
H
Bhan
A K
AK
Geha
R S
RS
D000485:Allergens / Q000276:immunology; D000818:Animals; D006224:Cricetinae; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin