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ToxSci Advance Access published online on April 20, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi177
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Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 31, 2005
Accepted April 14, 2005

Immunotoxiocology

Dose-dependent modulation of the in vitro cytokine production of human immune competent cells by lead salts

Nasr Y. A. Hemdan 1, Frank Emmrich 2, Khadiga Adham 3, Gunnar Wichmann 4, Irina Lehmann 4, Azza El-Massry 3, Hossam Ghoneim 3, Jörg Lehmann 5, and Ulrich Sack 2*

1 Institute of Clinical Immunology and Transfusion Medicine - IKIT, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany; Department of Environmental Immunology, UFZ-Centre for Environmental Research Leipzig-Halle, Permoserstraße 15, 04318 Leipzig, Germany
2 Institute of Clinical Immunology and Transfusion Medicine - IKIT, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany
3 Department of Zoology, Faculty of Science, University of Alexandria, Moharram Bey, Alexandria, Egypt
4 Department of Environmental Immunology, UFZ-Centre for Environmental Research Leipzig-Halle, Permoserstraße 15, 04318 Leipzig, Germany
5 Labor Diagnostik GmbH, Deutscher Platz 5b/BioCity, 04103 Leipzig, Germany

* To whom correspondence should be addressed.
Ulrich Sack, E-mail: ulrich.sack{at}medizin.uni-leipzig.de


  Abstract

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 twenty-four hours in 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)-{gamma}, interleukin (IL)-1{beta}, and tumour necrosis factor (TNF)-{alpha} 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, 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-{gamma} and the proinflammatory cytokines TNF-{alpha} and IL-1{beta}. 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.

Keywords: Allergy; autoimmune diseases; cytokine; immune response; lead salts; T helper cells.
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