Infection and immunity
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Infection and immunity · Mar 1992
Lipopolysaccharide-tumor necrosis factor-glucocorticoid interactions during cecal ligation and puncture-induced sepsis in mature versus senescent mice.
Previous work in our laboratory demonstrated increased sensitivity of senescent (24-month-old) mice to cecal ligation and puncture (CLP) sepsis compared with that of mature (12-month-old) mice. In this study the median lethal dose of the strain of Escherichia coli most frequently isolated during CLP sepsis was determined. No significant age-associated difference in the mean lethal dose or the mean survival time was noted; however, sham surgery before injection of E. coli decreased the mean lethal dose by at least 100-fold. ⋯ The amount of TNF produced locally in the peritoneum was also substantially higher in senescent mice than in mature animals (1,716 pg/ml versus 776 pg/ml). The increased production of TNF in senescent animals, despite elevated circulating corticosterone levels, suggested an age-related defect in glucocorticoid-directed downregulation of TNF production. This was confirmed in lipopolysaccharide-treated animals given exogenous dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS)