Neonatal Lead Exposure Potentiates Sickness Behavior Induced by Listeria monocytogenes Infection of Mice

Abstract

The effects of lead (Pb) administration on infection-induced decreases in water intake, food intake, and body weight gain have been assessed as manifestations of sickness behavior using a BALB/c mouse model. Pb acetate (0.5 mM) was administered via drinking water to dams from Day 0 postpartum to weaning and to mouse pups after weaning until sacrifice. At 22 days after birth, young mice were infected with Listeria monocytogenes. Mice with blood Pb levels of less than 25 μg/dl exhibited enhanced and prolonged sickness behavior compared to mice not exposed to Pb. With this mouse model, after infection, serum levels of interleukin (IL)-1β and IL-6 were enhanced in Pb-exposed mice. Compared with control infected mice, significant reductions in the number of thymic CD4+CD8+, CD4+, CD8+, and CD4−CD8− T cells were observed in Pb-exposed mice. As a substitute for the infection, mice were injected with IL-1 and/or IL-6; Pb exacerbated sickness behavior only in mice injected peripherally with IL-1 and IL-6. Our data in young mice suggest that children with blood Pb levels during bacterial infection may exhibit enhanced and prolonged sickness behavior due to Pb/cytokine-dependent processes and that Pb appears to influence sickness behavior depending on the types and amounts of cytokines generated.