Toxicology 132 (1999) 67–79 Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity Suping Chen, Karen A. Golemboski, Forrest S. Sanders, Rodney R. Dietert * Institute for Comparati6e and En6ironmental Toxicology, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell Uni6ersity, Ithaca, NY 14853 -6401, USA Received 16 April 1998; accepted 12 October 1998 Abstract 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), interferong (IFNg) production), enhanced a Th2-type response (interleukin-4 (IL-4) production), and increased tumor necrosis factor a (TNFa ) 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, TNFa, 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. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Immunotoxicity; Meso-2,3-dimercaptosuccinic acid (DMSA); Lead acetate * Corresponding author. Tel.: +1-607-2534015; fax: +1-607-2533384; e-mail: rrd1@cornell.edu. 0300-483X/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0300-483X(99)00139-5