Local but not systemic administration of IFN-gamma during the sensitization phase of protein antigen immunization suppress Th2 development in a murine model of atopic dermatitis.
Biphasic Th1/Th2 development plays a central role in the pathogenesis of atopic dermatitis. In the sensitization phase after protein antigen exposure, an immune response polarized toward Th2 differentiation, which is due to the hosts' genetic proneness to the disease, initiates the skin lesions. Th1/Th2 antagonism is a potential mechanism that could be manipulated to suppress the initial Th2 deviation. IL-12 is the key cytokine for Th1 differentiation. Interferon gamma (IFN-gamma) can assist Th1 development through several mechanisms and suppress Th2 differentiation. We took advantage of a recently developed murine model of atopic dermatitis elicited by epicutaneous sensitization with protein antigen through patch application to examine the effects of different routes of IFN-gamma administration on Th1/Th2 differentiation during the sensitization phase of antigen exposure. Our data showed that systemic administration of IFN-gamma during the sensitization phase could not promote serum levels of specific IgG(2a). However, local administration (intradermal injection or patch application) of IFN-gamma during the sensitization phase could promote serum levels of specific IgG(2a) and suppress serum levels of specific IgE. Moreover, pretreatment of local IFN-gamma with protein antigen has a long-term modulatory effect on serum levels of specific IgG(2a) and IgE after repeated antigen immunization. Our results demonstrate that local but not systemic administration of IFN-gamma during the sensitization phase of protein antigen immunization could suppress the Th2 deviation in this murine model of atopic dermatitis. Thus, this may represent a novel strategy for the treatment and prevention of atopic dermatitis.
Wang
Li-Fang
LF
Department of Dermatology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Wu
June-Tai
JT
Sun
Chee-Ching
CC
D000485:Allergens / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012867:Skin / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D007371:Interferon-gamma