ToxSci Advance Access originally published online on April 20, 2005
Toxicological Sciences 2005 86(1):75-83; doi:10.1093/toxsci/kfi177
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Dose-Dependent Modulation of the In Vitro Cytokine Production of Human Immune Competent Cells by Lead Salts
* Institute of Clinical Immunology and Transfusion Medicine—IKIT, University of Leipzig, D-04103 Leipzig, Germany; Department of Environmental Immunology, UFZ-Centre for Environmental Research Leipzig-Halle, D-04318 Leipzig, Germany; Department of Zoology, Faculty of Science, University of Alexandria, Moharram Bey, Alexandria, Egypt; Labor Diagnostik GmbH, D-04103 Leipzig, Germany
Received January 31, 2005; accepted April 14, 2005
Lead pollution constitutes a major health problem that has been intensively debated. To reveal its effects on the immune response, the influence of lead on the in vitro cytokine production of human peripheral mononuclear blood cells was investigated. Isolated cells were exposed to lead acetate or lead chloride for 24 h in the presence of either heat-killed Salmonella enteritidis (hk-SE) or monoclonal antibodies (anti-CD3, anti-CD28, anti-CD40) as cell activators. Our results showed that while higher lead doses are toxic, lower ones evoke immunomodulatory effects. All tested lead doses significantly reduced cell vitality and/or proliferation and affected secretion of proinflammatory, T helper cell type (TH)1 and TH2 cytokines. Expression of interferon (IFN)-
, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-
was reduced at lower lead doses in both models of cell stimulation. Although hk-SE failed to induce detectable IL-4 levels, monoclonal antibody–induced IL-4, IL-6, and IL-10 secretion increased in the presence of lower lead doses. Also, levels of hk-SE-induced IL-10 and IL-6 secretion were increased at lower lead doses. Thus, exposure to lower doses leads to suppression of the TH1 cytokine IFN- and the proinflammatory cytokines TNF- and IL-1ß. The elevated production of IL-4 and/or IL-10 can induce and maintain a TH2 immune response and might contribute to increased susceptibility to pathologic agents as well as the incidence of allergic hypersensitivity and/or TH2-dominated autoimmune diseases.
Key Words: allergy; autoimmune diseases; cytokine; immune response; lead salts; T helper cells.
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