title: The mechanism of a defective IFN-gamma response to bacterial toxins in an atopic dermatitis model, NC/Nga mice, and the therapeutic effect of IFN-gamma, IL-12, or IL-18 on dermatitis.
abstract: NC/Nga (NC) mice raised under conventional conditions (Conv. NC mice) spontaneously develop dermatitis similar to human atopic dermatitis, whereas NC mice raised under the specific pathogen-free conditions do not develop dermatitis. In the present study, we show that the representative Th1 cytokine, IFN-gamma levels in the sera of NC mice, injected with either staphylococcal enterotoxin B or endotoxin (LPS), to be severalfold lower than those of normal mice. The low IFN-gamma response to staphylococcal enterotoxin B was correlated to the lack of regular Vbeta8(+) T cells and Vbeta8(+) NK T cells, and the low IFN-gamma response to LPS was correlated to an impaired IL-18 production of macrophages. The CD3-stimulated IL-4 production from liver and spleen T cells from Conv. NC mice in vitro was greatly augmented. The serum IL-4 levels of untreated Conv. NC mice also were higher than those of normal mice and specific pathogen-free NC mice. Treatment of Conv. NC mice either with IFN-gamma, IL-12, or IL-18 twice a week from 4 wk of age substantially inhibited the elevation of the serum IgE levels, serum IL-4 levels, and dermatitis, and IL-12 or IL-18 treatment also reduced the in vitro IL-4 production from CD3-stimulated liver T cells. The systemic deficiency in the Th1 response to bacterial stimulation thus leads to a Th2-dominant state and may induce an abnormal cellular immune response in the skin accompanied with an overproduction of IgE and a susceptibility to dermatitis in NC mice.
authors: Division of Basic Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan.
authors: Y
authors: Y
authors: Habu
authors: S
authors: S
authors: Seki
authors: E
authors: E
authors: Takayama
authors: T
authors: T
authors: Ohkawa
authors: Y
authors: Y
authors: Koike
authors: K
authors: K
authors: Ami
authors: T
authors: T
authors: Majima
authors: H
authors: H
authors: Hiraide
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology / Q000517:prevention & control*; D004198:Disease Susceptibility; D004768:Enterotoxins / Q000008:administration & dosage*; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency* / Q000627:therapeutic use; D018664:Interleukin-12 / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000096:biosynthesis / Q000172:deficiency / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000172:deficiency; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D004768:Enterotoxins; D007106:Immune Sera; D020382:Interleukin-18; D008070:Lipopolysaccharides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018664:Interleukin-12; D015847:Interleukin-4; C026066:enterotoxin A, Staphylococcal; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma