Lead differentially modifies cytokine production in vitro and in vivo.
An imbalance between helper T cell type 1 (Th1) and helper T cell type 2 (Th2) activation can result in immunodysregulations leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant humoral immunity that may culminate with an autoimmune disease. Mercury, a heavy-metal toxicant, is known to induce renal autoimmunity characterized by a predominant Th2 response. Lead, another metal toxicant, causes enhanced B cell activities and impairs host resistance to several bacterial and viral infections. In addition, Pb was reported to enhance Th2 proliferation and inhibit Th1 proliferation. The differential effects of Pb on Th subset activation have been further investigated. In vitro IL-4 production by a Th2 clone was significantly increased by the addition of PbCl2, whereas IFN gamma production by a Th1 clone was decreased by the addition of PbCl2. When BALB/c mice were subcutaneously exposed to PbCl2, ex vivo Il-4 production by anti-CD3-stimulated splenic T cells was enhanced, but IFN gamma production was inhibited. Additionally, the plasma IL-4 and IgE levels of Pb-exposed mice were increased, and the plasma IFN gamma levels were significantly lowered in the absence of any additional exogenous antigen. In vitro, ex vivo, and in vivo treatment with HgCl2 produced similar findings. This study is the first report of the preferential activation of a Th2 response by Pb in vivo and suggests that PB, like Hg, may induce autoimmune responses by upsetting the balance between Th1- and Th2-like cells, which could enhance production of antibodies to self antigens.
Heo
Y
Y
Wadsworth Center, New York State Department of Health, Albany 12201, USA.
Parsons
P J
PJ
Lawrence
D A
DA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D008213:Lymphocyte Activation; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D015847:Interleukin-4; D007854:Lead; D007073:Immunoglobulin E; C029891:lead chloride; D008627:Mercuric Chloride; D007371:Interferon-gamma