Assessment of immunotoxicity parameters in individuals occupationally exposed to lead.
Although adverse health effects produced by lead (Pb) have long been recognized, studies regarding the immunotoxic effects of occupational exposure report conflicting results. In a previous study, alterations in some immunological parameters were noted in 70 Pb-exposed workers. In view of these results, it was of interest to extend this study comprising a larger population and increasing the number of immunological endpoints assessed. Accordingly, in this study the immunotoxic effects of occupational exposure to Pb were assessed by analyzing (1) percentages of lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD19⁺, and CD56⁺/16⁺); (2) concentration of plasma cytokines, namely, interleukin (IL) 2, IL4, IL6, IL10, tumor necrosis factor (TNF) α, and interferon (IFN) γ; and (3) plasma concentrations of neopterin, tryptophan (Trp), and kynurenine (Kyn). In addition, the possible influence of genetic polymorphisms in the vitamin D receptor (VDR) and δ-aminolevulinic acid dehydratase (ALAD) genes on immunotoxicity parameters was studied. Exposed workers showed significant decreases in %CD3⁺, %CD4⁺/%CD8⁺ ratio, IL4, TNFα, IFNγ, and Kyn to Trp ratio (Kyn/Trp), and significant increases in %CD8⁺, IL10, and Trp levels. All these parameters, except Trp, were significantly correlated with exposure biomarkers. No significant influence of genetic polymorphisms was observed. Significant correlation between Kyn/Trp and neopterin concentrations suggests an involvement of indoleamine 2,3-dioxygenase in the Trp metabolic alterations, which may contribute to some of the immune alterations observed. Results obtained suggest that occupational exposure to PB may influence the immune system by impairing several mechanisms, which might ultimately produce deregulation of the immune response and diminish immunosurveillance in exposed individuals.
Toxicology Unit, Department of Psychobiology, University of A Coruña, A Coruña, Spain. jgarciale@udc.es
Julia
J
García-Lestón
Joana
J
Roma-Torres
Olga
O
Mayan
Sebastian
S
Schroecksnadel
Dietmar
D
Fuchs
Ana O
AO
Moreira
Eduardo
E
Pásaro
Josefina
J
Méndez
João Paulo
JP
Teixeira
Blanca
B
Laffon
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D056726:Genetic Association Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000633:toxicity*; D007221:Industry; D007737:Kynurenine / Q000097:blood; D007854:Lead / Q000097:blood / Q000633:toxicity*; D007855:Lead Poisoning / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000097:blood / Q000235:genetics; D011174:Portugal; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics; D012907:Smoking / Q000097:blood; D013030:Spain; D014364:Tryptophan / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D018167:Receptors, Calcitriol; D007854:Lead; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D000623:Porphobilinogen Synthase