title: Developmental windows of differential lead-induced immunotoxicity in chickens.
abstract: The developing immune system of rodents has been shown to exhibit increased sensitivity to lead-induced immunotoxicity compared with that of adults. However, little is known about potential windows of increased vulnerability during discrete periods of embryonic development. To investigate differential embryonic sensitivity to lead-induced immunotoxicity, sublethal doses of lead ranging from 5 to 400 microg/egg were introduced into fertilized Cornell K Strain White Leghorn chicken eggs via the air sac at one of four different stages of embryonic development (5, 7, 9, and 12 days of incubation, designated as E5, E7, E9, and E12, respectively). Lead levels of blood and bone were determined at hatching and lead-induced immunotoxicity was evaluated in 5-6 week old young chickens using a delayed-type hypersensitivity (DTH) reaction against bovine serum albumin (BSA), macrophage production of nitric oxide, and interferon-gamma (IFN-gamma) production by splenic lymphocytes as immune indicators. Splenic lymphocyte production of IFN-gamma was significantly suppressed (measured for E7 and E9 exposures only, P<0.05) among lead treated groups when compared with controls. Macrophage production of nitric oxide (measured as nitrite production) was significantly depressed (P<0.05) following E5, E7, and E9 lead exposures but not following E12 lead exposure. In contrast with this pattern, DTH function was unaltered following the E5, E7, and E9 exposures, but was significantly depressed (P<0.05) after E12 exposure to lead. Since the same lead dose (200 microg/egg) given at E9 and E12 produced the same blood and bone lead levels and resulted in a different outcome regarding DTH function, the capacity of lead to influence DTH function appeared to emerge between days 9 and 12 of in ovo development. Based on these results, it is hypothesized that lead exposure during different windows of embryonic development is likely to result in different immunotoxic outcomes in the juvenile.
authors.affiliation: Department of Microbiology and Immunology, Institute for Comparative and Environmental Toxicology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: K A
authors.initials: KA
authors.lastname: Golemboski
authors.forename: P J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: R R
authors.initials: RR
authors.lastname: Dietert
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002642:Chick Embryo; D005260:Female; 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; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010533:Peritoneal Lavage; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D007854:Lead; D009569:Nitric Oxide; D007371:Interferon-gamma