Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity.
Meso-2,3-dimercaptosuccinic acid (DMSA) is a drug currently employed for cheltion therapy in lead poisoning; however, little is known about its potential effects on the immune system. To examine the effect of DMSA and its capacity to reverse immunotoxicity resulting from exposure to lead in utero, female Fischer 344 rats were administered lead acetate in drinking water from 2 weeks prior to mating until parturition; DMSA was given by gavage on days 6-21 of gestation. The immune function of the female offspring was tested at 13 weeks of age. The results showed that lead (250 ppm) suppressed Th1-type responses (delayed-type hypersensitivity (DTH), interferon gamma (IFN gamma) production), enhanced a Th2-type response (interleukin-4 (IL-4) production), and increased tumor necrosis factor alpha (TNF alpha) production from macrophages. DMSA treatment (60 mg/kg per day) during pregnancy significantly lowered the blood lead levels of both the embryos and the lactating dams as well as the milk lead level of lactating dams. The chelation treatment also reversed the lead-induced alterations in pup body weight, relative spleen weight, TNF alpha, and IL-4 production. But in utero exposure to DMSA alone resulted in decreased DTH response in adult offspring. This was likely due to a reduced cell recruitment, since plasma monocyte chemoattractant protein-1 (MCP-1) levels were decreased. The DMSA-exposed offspring also demonstrated increased interleukin-2 (IL-2) production. These results suggest that DMSA reverses some of the lead-induced immunotoxicity; however, this treatment itself during embryonic development produces subsequent adult immunomodulation.
Chen
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Institute for Comparative and Environmental Toxicology, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA.
Golemboski
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Sanders
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FS
Dietert
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RR
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007107:Immune System / Q000187:drug effects*; D007774:Lactation / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008892:Milk / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000276:immunology; D004113:Succimer / Q000494:pharmacology*
D000931:Antidotes; D002614:Chelating Agents; D016207:Cytokines; D007854:Lead; D004113:Succimer