Dose-dependent modulation of the in vitro cytokine production of human immune competent cells by lead salts.
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 (T(H))1 and T(H)2 cytokines. Expression of interferon (IFN)-gamma, interleukin (IL)-1beta, and tumor 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, 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 T(H)1 cytokine IFN-gamma and the proinflammatory cytokines TNF-alpha and IL-1beta. The elevated production of IL-4 and/or IL-10 can induce and maintain a T(H)2 immune response and might contribute to increased susceptibility to pathologic agents as well as the incidence of allergic hypersensitivity and/or T(H)2-dominated autoimmune diseases.
Hemdan
Nasr Y A
NY
Institute of Clinical Immunology and Transfusion Medicine--IKIT, University of Leipzig, D-04103 Leipzig, Germany.
Emmrich
Frank
F
Adham
Khadiga
K
Wichmann
Gunnar
G
Lehmann
Irina
I
El-Massry
Azza
A
Ghoneim
Hossam
H
Lehmann
Jörg
J
Sack
Ulrich
U
D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D009942:Organometallic Compounds; D007854:Lead; C029891:lead chloride; C008261:lead acetate