Developmental immunotoxicity of lead in the rat: influence of maternal diet

The effect of maternal dietary protein intake on lead-induced developmental immunotoxicity was studied in female Fischer 344 rats receiving lead acetate (250 ppm) or sodium acetate (control) in the drinking water during breeding and pregnancy until parturition. Dams were fed isocaloric diets (either 20% casein or 10% casein) from 2 wk prior to mating until the end of lactation. After weaning, dams and female offspring were given the 20% casein diet and regular water. Immune function was assessed in dams at 8 wk postpartum and in offspring at 13 wk of age. Dams showed no marked difference in any of the immune endpoints examined, regardless of diet or lead treatment. In contrast, lead exposure during early development produced a subsequent significant reduction of both the delayed-type hypersensitivity response and interferon gamma production in adult offspring independent of maternal diet. Lead-exposed offspring from the high-dietary-protein group had significantly elevated production of both interleukin-4 and tumor necrosis factor alpha(TNF-alpha) with increased relative spleen weight and a decreased body weight compared to offspring in the lead control group. In contrast, lead-exposed offspring from dams receiving the low-protein diet had no marked change in TNF-alpha levels, relative spleen weight, or body weight, while interleukin-4 levels were significantly reduced compared with the lead control group. In conclusion, maternal dietary protein intake can modulate the immunotoxic effects of lead exposure during early development. This occurred at levels of protein intake and doses of lead exposure that produced no detectable effect on the maternal immune system.