Effects of aging on mortality, hypothermia, and cytokine induction in mice with endotoxemia or sepsis

Hiroshi Saito, Edward R. Sherwood, Tushar K. Varma, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

Aging is accompanied by an altered stress response that underlies increased susceptibility of the elderly patients to physiological stress such as infection and sepsis. In the present study, we investigated the effects of aging on mortality, hypothermia, and cytokine induction in mouse models of intra-abdominal sepsis and endotoxemia. Systemic inflammation associated with either cecal ligation/puncture (CLP) or injection with bacterial endotoxin, lipopolysaccharide (LPS), resulted in a significantly elevated mortality rate in aged (24 months) compared to young (4 months) mice. The aged mice also showed profound hypothermia during these inflammatory stresses; the severity of hypothermia at the early phase of sepsis or endotoxemia could predict the mortality of individual animals. The stress-mediated induction of interleukin-1β, interleukin-6, and interleukin-10 (IL-1β, IL-6, and IL-10) in the circulating blood tended to be higher with aging in both CLP and LPS models, and in particular, the induction of IL-6 was significantly augmented with aging. The serum level of IL-6 showed a strong correlation with degrees of hypothermia. In the heart and lungs, the induction of mRNA for IL-6 and IL-10 was also significantly enhanced with aging. These results clearly demonstrate an age-associated increase in mortality, hypothermia, and induction of IL-6 during endotoxemia and sepsis.

Original languageEnglish
Pages (from-to)1047-1058
Number of pages12
JournalMechanisms of Ageing and Development
Volume124
Issue number10-12
DOIs
StatePublished - Dec 2003

Bibliographical note

Funding Information:
We thank Jacalyn Johnson and Cheng-Yie Lin for technical assistance, and Karen Martin for manuscript preparation. This work was supported by grants R37 AG10885 and 5P01 DK35608 from the National Institutes of Health.

Keywords

  • Aging
  • Cytokines
  • Endotoxemia
  • Hypothermia
  • Sepsis

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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