title: The paradoxical effects of lead in interferon-gamma knockout BALB/c mice.
abstract: It has been reported that lead (Pb) exposure enhances interleukin (IL)-4 and inhibits interferon-gamma (IFNgamma) production in wild-type (WT) BALB/c mice. Here, we examined Pb effects on immunity in IFNgamma knockout (KO) mice. Lead significantly enhanced serum IgG1 anti-keyhole limpet hemocyanin (KLH) levels in WT mice compared to the controls; Pb also increased serum IgG2a anti-KLH levels, but the IgG1:IgG2a ratio was greater with Pb. In addition, total serum IgE levels, but not IgE anti-KLH levels, were increased. In the KO mice, the serum IgG1, IgG2a, IgE anti-KLH, and total IgE levels were significantly lower than those of WT mice. Surprisingly, Pb significantly enhanced IgG1 and IgG2a anti-KLH levels in the KO mice. However, for these mice, unlike the WT mice, Pb caused a greater percentage change in IgG2a than in IgG1 anti-KLH, indicating less skewing toward type-2 immunoglobulins. Lead also enhanced the delayed-type hypersensitivity (DTH) response in WT mice. Not surprisingly, very low DTH occurred in the KO mice; however, Pb induced a strong KLH-specific DTH response. The in vivo Pb exposure significantly increased in vitro production of IL-4, IL-5, and IL-10, but not IFNgamma, IL-2 and IL-12, by KLH-induced WT and KO spleen cells. In contrast to KLH, dinitrofluorobenzene contact hypersensitivity (DNFB CHS) was detected in all groups, and Pb did not affect this response, which suggests that Pb has only a slight effect on CD8+ T cell-related responses. As previously reported, Pb enhances Th2 responses in WT mice; however, in the KO mice, Pb enhanced Th1-related anti-KLH production and a Th2-related DTH. The Pb enhancement of DTH in IFNgamma-deficient mice is likely due to promotion of type-2 cytokines and enhancement of major histocompatibility complex (MHC) class II expression.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Donghong
authors.initials: D
authors.lastname: Gao
authors.forename: Jane
authors.initials: J
authors.lastname: Kasten-Jolly
authors.forename: David A
authors.initials: DA
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics*; D007854:Lead / Q000633:toxicity*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007854:Lead; D007073:Immunoglobulin E; C029891:lead chloride; D007371:Interferon-gamma