Below background levels of blood lead impact cytokine levels in male and female mice.
A number of studies have documented that Pb exerts immunotoxic effects on T lymphocytes. In studies designed to explore this general response over a broad dose range, female Swiss mice were administered six different diets containing Pb acetate 1 day after mating. During lactation, the mothers received the same feed given during pregnancy, and the same diets were administered to the offspring for 9 months after weaning. At the end of exposure, blood Pb level in the offspring was determined, and possible changes in two type 1 cytokines (IL-2, INF-gamma) and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb levels (40 and 400 ppm), a significant increase in IL-4 production was associated with a profound decrease in INF-gamma and IL-2 production. At the lowest Pb diet level (0.02 ppm), which resulted in a blood lead level of (0.8 microg/dL), which is below background (2-3 microg/dL) values in humans, increases in INF-gamma and IL-2 production along with a significant decrease in IL-4 production were observed. The findings provide evidence of a reversal of lead-induced cytokine skewing depending on the blood lead concentration. As blood lead concentration increases, there is a notable skewing toward Th2, while the pattern is reversed favoring Th1 development at lower blood lead values. The present findings are also notable since they indicate the potential for dietary Pb to have significant biological effects below normal background concentrations.
Iavicoli
I
I
Institute of Occupational Health, Catholic University of Sacred Heart, School of Medicine, Largo Francesco Vito, 1, 00168 Roma, Italy. iavicoli.ivo@rm.unicatt.it
Carelli
G
G
Stanek
E J
EJ
Castellino
N
N
Calabrese
E J
EJ
D000284:Administration, Oral; D000818:Animals; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D007371:Interferon-gamma / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood*; D007854:Lead / Q000097:blood* / Q000633:toxicity; D008297:Male; D051379:Mice; D012737:Sex Factors
D007376:Interleukin-2; D015847:Interleukin-4; D007854:Lead; D007371:Interferon-gamma