Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity

Chen, Suping; Golemboski, Karen A.; Sanders, F. S.; Dietert, Rodney R.

doi:10.1016/s0300-483x(98)00139-5

Cited by 60 publications

(21 citation statements)

References 39 publications

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“…The primary effect on T cells is a shift in the T helper (Th) cell functional balance, with Thl function depressed and Th2 function elevated (15). In a dose-response comparison among pregnant rats and rat female pups exposed during gestation and assessed as young adults, developing fetuses were susceptible to persistent immunotoxic effects of lead at doses that did not affect the pregnant dams (21,22). The nature of the immunotoxicity was similar to that reported for exposed adults; rats exposed in utero exhibited depressed Th 1 function (e.g., reflected by a depressed DTH response) with a concomitant elevation in some Th2-dependent parameters.…”

Section: The Immune Systemmentioning

confidence: 99%

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Dietert

Etzel

Chen

et al. 2000

Environ Health Perspect

226

122

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Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment.

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Section: The Immune Systemmentioning

confidence: 99%

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Dietert

Etzel

Chen

et al. 2000

Environ Health Perspect

226

122

View full text Add to dashboard Cite

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“…Previous studies have shown that lead can increase susceptibility to infectious agents (Selye et al 1966;Hemphil et al 1971;Cook et al 1975;Gainer 1974Gainer , 1977Exon et al 1979;Lawrence 1981;Kowolenko et al 1991;Youssef et al 1996), as well as incidence and/or growth of tumors (Gainer 1973;Kobayashi and Okamoto 1974;Kerkvliet and Baecher-Steppan 1982). Lead appears to impair helper T lymphocyte function and regulatory processes leading to aberrant cell-mediated immunity and/or humoral immunity (McCabe and Lawrence 1991;Heo et al 1996Heo et al , 1998Miller et al 1998;Chen et al 1999; Lee et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Embryonic exposure to lead: comparison of immune and cellular responses in unchallenged and virally stressed chickens

et al. 2001

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Lead, a ubiquitous environmental contaminant, has been shown to modulate various functions of the immune system and decrease host resistance to infectious disease. However, limited information is available concerning the direct effects of lead on the host immune response to an infectious agent after developmental exposure. The current study utilized chickens to examine the effect of embryonic lead exposure on immune and cellular responses during viral challenge. Sublethal doses of lead were introduced into fertilized Cornell K Strain White Leghorn chicken eggs via the air sac at day 5 or day 12 of embryonic development (designated as E5 and E12, respectively). Four-week-old female chickens were inoculated with infectious bronchitis virus (IBV) strain M41. Antibody titer to IBV, delayed-type hypersensitivity (DTH) response against bovine serum albumin (BSA), the absolute number and percentage of leukocyte subpopulations, and interferon-gamma (IFN-gamma)-like cytokine production by splenocytes were evaluated at 5-6 weeks of age. While antibody response to IBV in juvenile chicks was unaffected by the in ovo lead exposure, IFN-gamma-like cytokine production by splenocytes was significantly depressed following lead exposure at both developmental stages. In contrast with this pattern, the DTH response against BSA was unaffected following E5 exposure, but was significantly decreased after E12 exposure to lead. These changes were similar to those previously reported in chickens not exposed to IBV. While lead exposure at E5 induced significant changes in the percentage of circulating heterophils at 1 day postinfection (dpi), lead did not cause any change in relative leukocyte counts after E12 exposure. At 7 dpi, E5 lead exposure resulted in decreased absolute number and percentage of circulating lymphocytes, while total leukocyte counts, and the absolute number and percentage of circulating monocytes and heterophils were significantly reduced in E12 lead-exposed chickens. These results suggest that low-level exposure to lead has a direct effect on the developing chicken immune system, which is evident even during a postnatal infection. Furthermore, some of the changes were observed only when chicks were stressed by the viral infection. It appears that lead exposure during different stages of embryonic development is likely to result in different immunotoxic outcomes in juveniles.

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“…The immune function of the female offspring was tested at 13 weeks of age. The results showed that lead suppressed Th1-type responses delayed type hypersensitivity, IFN-γ production, enhanced a Th2-type response IL-4 production, and increased TNF-α production from macrophages (Chen et al, 1999). 3.15 ± 0.52 g**; h** C -control; I -infested by A. suum eggs; E -exposed to lead acetate trihydrate; EI -exposed to lead acetate trihydrate and infested by A. suum eggs; * p < 0.05; ** p < 0.01; *** p < 0.001; Significant difference between groups: a** -C and E; b** -C and EI; c*** -I and E; e** -C and I; f*** -I and E; d***, g** -I and EI; h** -E and EI h** C -control; I -infested by A. suum eggs; E -exposed to lead acetate trihydrate; EI -exposed to lead acetate trihydrate and infested by A. suum eggs; * p < 0.05; ** p < 0.01; *** p < 0.001; Significant difference between groups: a** -C and E; b** -C and EI; c**, g*** -I and E; d**, h** -I and EI; e* -C and I; f** -C and E A number of studies have documented that lead exerts immunotoxic effects on T-lymphocytes.…”

Section: Discussionmentioning

confidence: 97%

“…This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases (Dietert et al, 2004). The persistent effect of lead acetate-induced immunotoxicity was studied by Chen et al (1999). Female Fischer 344 rats were administered 250 ppm lead acetate in drinking water from 2 weeks prior to mating until parturition.…”

Section: Discussionmentioning

confidence: 99%

The effect of chronic lead acetate trihydrate intoxication in Wistar rats on experimental Ascaris suum infestation and immunity

et al. 2008

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SummarySPF male Wistar rats were exposed for four months to lead acetate trihydrate present in drinking water (100 mg/l) and subsequently infested with 1000 ± 100 infective A. suum eggs. Metabolic activity of phagocytes and proliferative activity of T-lymphocytes were investigated on Day 4 and 8 after A. suum eggs infestation (Day 130 and 134 of lead acetate trihydrate exposition). The results demonstrated that treatment with lead acetate trihydrate led to increased susceptibility to infestation, manifested by increased average number of A. suum larvae in the lungs of exposed rats compared to unexposed ones. Moreover, migration of A. suum larvae on Day 8 was associated with significant increase in index of metabolic activity of phagocytes in unexposed rats in comparison with controls. In contrast, in rats exposed to the lead and infested by A. suum eggs a non-significant increase in the studied immunological parameters was recorded. Significant differences in immunological parameters were observed between unexposed, infested and infested and exposed groups of rats. In the unexposed group of animals Ascaris suum infestation caused a significant increase in the index of metabolic activity of phagocytes and stimulation index of lymphocytes in comparison with lead exposed rats.

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Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity

Cited by 60 publications

References 39 publications

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Embryonic exposure to lead: comparison of immune and cellular responses in unchallenged and virally stressed chickens

The effect of chronic lead acetate trihydrate intoxication in Wistar rats on experimental Ascaris suum infestation and immunity

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