Detection of low-level environmental chemical allergy by a long-term sensitization method.
Multiple chemical sensitivity (MCS) is characterized by various signs, including neurological disorders and allergy. Exposure may occur through a major event, such as a chemical spill, or from long-term contact with chemicals at low levels. We are interested in the allergenicity of MCS and the detection of low-level chemical-related hypersensitivity. We used long-term sensitization followed by low-dose challenge to evaluate sensitization by well-known Th2 type sensitizers (trimellitic anhydride (TMA) and toluene diisocyanate (TDI)) and a Th1 type sensitizer (2,4-dinitrochlorobenzene (DNCB)). After topically sensitizing BALB/c mice (9 times in 3 weeks) and challenging them with TMA, TDI or DNCB, we assayed their auricular lymph nodes (LNs) for number of lymphocytes, surface antigen expression of B cells, and local cytokine production, and measured antigen-specific serum IgE levels. TMA and TDI induced marked increases in levels of antigen-specific serum IgE and of Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) produced by ex vivo restimulated lymph node cells. DNCB induced a marked increase in Th1 cytokine (IL-2, IFN-gamma, and TNF-alpha) levels, but antigen-specific serum IgE levels were not elevated. All chemicals induced significant increases in number of lymphocytes and surface antigen expression of B cells. Our mouse model enabled the identification and characterization of chemical-related allergic reactions at low levels. This long-term sensitization method would be useful for detecting environmental chemical-related hypersensitivity.
Institute of Environmental Toxicology, Ibaraki 303-0043, Japan. fukuyama@iet.or.jp
Tomoki
T
Fukuyama
Hideo
H
Ueda
Koichi
K
Hayashi
Yukari
Y
Tajima
Yasufumi
Y
Shuto
Toru R
TR
Saito
Takanori
T
Harada
Tadashi
T
Kosaka
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018777:Multiple Chemical Sensitivity / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010796:Phthalic Anhydrides / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D004137:Dinitrochlorobenzene; D010796:Phthalic Anhydrides; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E; C015559:trimellitic anhydride