Effects of aging on the immunopathologic response to sepsis

Abstract

Objective-Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine if this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts.Design-Prospective, randomized controlled study.Setting-Animal laboratory in a university medical center.Subjects-Young (6-12 week) and aged (20-24 month) FVB/N mice.Interventions-Mice were subjected to 2×25 or 1×30 cecal ligation and puncture (CLP). Measurements and MainResults-Survival was similar in young mice subjected to 2×25 CLP and aged mice subjected to 1×30 CLP (p=0.15). Young mice subjected to 1×30 CLP had improved survival compared to both other groups (p<0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of TNF-α, IL-6, IL-10 and MCP-1 were elevated 24 hours after CLP in aged animals compared to young animals (p<0.05). When mortality was similar but injury severity was different, there were no significant differences in systemic cytokines between aged mice and young mice. In contrast, peritoneal levels of TNF-α, IL-6, and IL-10 were higher in aged mice subjected to 1×30 CLP than young mice subjected to 2×25 CLP despite their similar mortalities (p<0.05). There were no significant differences in either bacteremia or peritoneal cultures when animals of different ages sustained similar injuries or had different injuries with similar mortalities.Conclusions-Aged mice are more likely to die from sepsis than young mice when subjected to an equivalent insult, and this is associated with increases in both systemic and local inflammation. There is an exaggerated local but not systemic inflammatory response in aged mice compared to young mice when mortality is similar. This suggests that systemic processes that culminate in death may be age-independent, but the local inflammatory response may be greater with aging.

Dysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages

“…Age-associated defects in LPSinduced IL-6 and TNFa are observed in the activation of all of these cell types (Gomez et al, 2007(Gomez et al, , 2009Turnbull et al, 2009). It is conceivable that age-associated in vivo defects in macrophage cytokine production can be reconciled with a proinflammatory environment that may result in enhanced basal levels of cytokines and chemokines.…”

The future of murine sepsis and trauma research models

“…For example, sepsis is an increasingly significant problem throughout the world, and infections remain 1 of the top causes of poor outcomes [1,2]. Severe sepsis and septic shock have estimated in-hospital mortalities of 29-40% and .50%, respectively [3][4][5].…”

Molecular Mechanism Responsible for the Priming of Macrophage Activation

“…Humans with these adverse conditions tend to have elevated mortality associated with septic shock (13,14). Endotoxin priming and exacerbated mortality are also observed in experimental animals (15,16).…”