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 ch eltion therapy in lead poisoning; however, little is known about its potent ial effects on the immune system. To examine the effect of DMSA and its cap acity to reverse immunotoxicity resulting from exposure to lead in utero, f emale Fischer 344 rats were administered lead acetate in drinking water fro m 2 weeks prior to mating until parturition; DMSA was given by gavage on da ys 6-21 of gestation. The immune function of the female offspring was teste d 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) pro duction), and increased tumor necrosis factor alpha (TNF alpha) production from macrophages. DMSA treatment (60 mg/kg per day) during pregnancy signif icantly 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 treat ment also reversed the lead-induced alterations in pup body weight, relativ e spleen weight, TNFa, and IL-4 production. But in utero exposure to DMSA a lone resulted in decreased DTH response in adult offspring. This was likely due to a reduced cell recruitment, since plasma monocyte chemoattractant p rotein-1 (MCP-1) levels were decreased. The DMSA-exposed offspring also dem onstrated increased interleukin-2 (IL-2) production. These results suggest that DMSA reverses some of the lead-induced immunotoxicity; however, this t reatment itself during embryonic development produces subsequent adult immu nomodulation. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.