Developmental immunotoxicity of lead: impact on thymic function.
BACKGROUND
Since the potential effects of early exposure to lead on thymic functions have not been fully characterized, in this study we evaluated the capacity of lead to alter thymic function in juvenile chickens following embryonic exposure.


METHODS
Cornell K strain White Leghorn chicken eggs were administered lead acetate (400 microg/egg) or sodium acetate (control) on embryonic development (E12) with and without thymulin supplementation. Ex vivo production of interferon-gamma (IFN-gamma)-like cytokine by thymocytes and a delayed-type hypersensitivity (DTH) reaction were measured in the juvenile. Additionally, the effects of in vitro exposure to lead on both thymocytes and thymic stromal cells (TSCs) were evaluated.


RESULTS
Following E12 exposure to lead, ex vivo production of IFN-gamma-like cytokine by juvenile-derived thymocytes decreased significantly compared to the control. The same effect was observed when thymocytes were directly exposed to lead in vitro and stimulated with thymic stromal supernatant. In contrast, when TSCs were exposed to lead in vitro, no change was seen in their functional capacity for promoting cytokine production. In ovo supplementation with thymulin partially reversed lead-induced DTH depression without any change in IFN-gamma-like cytokine production. Embryonic exposure to thymulin alone partially depressed the DTH response.


CONCLUSIONS
These results suggest that lead can directly influence thymocyte function in the absence of the thymic microenvironment. Since thymulin levels may influence lead-induced immunotoxicity, embryonic endocrine status may be an important consideration. Lead exposure appears to alter thymic functions directly; however, indirect effects via endocrine factors are not precluded.
Lee
Ji-Eun
JE
Institute for Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853, USA.
Dietert
Rodney R
RR
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004338:Drug Combinations; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007107:Immune System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D007109:Immunity / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013723:Teratogens / Q000493:pharmacokinetics / Q000633:toxicity*; D013935:Thymic Factor, Circulating / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development
D004338:Drug Combinations; D009942:Organometallic Compounds; D013723:Teratogens; D007371:Interferon-gamma; D013935:Thymic Factor, Circulating; C008261:lead acetate