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

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.