Differential sensitivity to endotoxin exposure in young and middle-age mice

Aging can have a profound effect on the neurobehavioral response to immune activation; aged subjects are predisposed to greater deficits in performance and cognitive function in conjunction with an exaggerated neuroinflammatory response. While increased reactivity to an immune insult has been well characterized in aged subjects, the alterations that may exist by middle-age have not been thoroughly investigated. The present study compared the reactions of young (4-month) and middle-age (12-month) male BALB/c mice to an acute or repeated lipopolysaccharide (LPS) challenge(s). The data suggest that in some respects middle-aged mice are more sensitive to endotoxin exposure, as they show enhanced weight loss, splenic cytokine levels, and c-fos expression in the brain following acute LPS administration compared to younger mice. However, acute LPS exposure led to comparable decreases in locomotor activity in young and middle-aged mice. Following repeated LPS administration both age groups showed diminished behavioral and neural reactions to the final LPS challenge, indicating tolerance development. However, the immune system of the middle-aged mice was still mildly responsive to the final LPS exposure, as splenic levels of IL-1beta were significantly elevated. Collectively, the data suggest that middle-age subjects are more sensitive to an immune insult.