Newborn mice differ from adult mice in chemokine and cytokine expression to ozone, but not to endotoxin

Neonatal animals of some mammalian species are more tolerant to several pul monary oxidative stress-inducing toxicants than adults. Our initial studies during hyperoxic injury demonstrated a rapid chemokine and cytokine respon se early in the development of injury in newborn mice, whereas adult mice d emonstrated little alteration in cytokine abundance until lethality was imm inent. Our hypothesis is that altered response between newborn and adult mi ce is associated with differential cell injury, rather than alterations in the regulation of the inflammatory response. To test this hypothesis we uti lized two distinct models of inducing pulmonary toxicity. ozone (O-3), whic h causes epithelial cell injury, and endotoxin, which causes pulmonary infl ammation independent of direct epithelial cell injury. C57BI/6J mice (36 h or 8 wk old) were exposed to O-3 at 7 or 2.5 ppm for 4, 20, or 24 h or to a 10-min inhalation of 10 ng endotoxin per mouse (estimated deposited dose) and were examined 2, 6, or 24 h postexposure. Adult mice displayed increase d sensitivity to O-3 as demonstrated by increased abundance of mRNAs encodi ng eotaxin, macrophage inflammatory protein (MIP)-1 alpha, MIP-2, interleuk in (IL)-6, and metallothionein (Mt). In newborn mice, only Mt was increased after 4 h of exposure. In contrast, newborn and adult mice responded simil arly at 2 h post endotoxin exposure, inducing messages encoding tumor necro sis factor (TNF)-alpha eotaxin, MIP-1 alpha; MIP-I beta, MIP-2, interferon inducible protein (IP)-10, and monocyte chemoatrractant protein (MCP)-1. Fu rthermore, interleukin-6 (IL-6) was increased in adults but not newborns. S imilar chemokine and cytokine responses of newborn and adult mice in respon se to an agent not causing epithelial injury (endotoxin) suggest that alter ed inflammatory control observed between newborn and adult mice following O -3 exposure is secondary to epithelial cell injury.