OBJECTIVE: Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine whether 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 weeks) and aged (20-24 months) FVB/N mice. INTERVENTIONS: Mice were subjected to 2 x 25 or 1 x 30 cecal ligation and puncture (CLP). MEASUREMENTS AND MAIN RESULTS: Survival was similar in young mice subjected to 2 x 25 CLP and aged mice subjected to 1 x 30 CLP (p = 0.15). Young mice subjected to 1 x 30 CLP had improved survival compared with the other groups (p < 0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and monocyte chemotactic protein-1 were elevated 24 hours after CLP in aged animals compared with 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 tumor necrosis factor-alpha, IL-6, and IL-10 were higher in aged mice subjected to 1 x 30 CLP than young mice subjected to 2 x 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 of 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 with 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.
OBJECTIVE: Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine whether 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 weeks) and aged (20-24 months) FVB/N mice. INTERVENTIONS:Mice were subjected to 2 x 25 or 1 x 30 cecal ligation and puncture (CLP). MEASUREMENTS AND MAIN RESULTS: Survival was similar in young mice subjected to 2 x 25 CLP and aged mice subjected to 1 x 30 CLP (p = 0.15). Young mice subjected to 1 x 30 CLP had improved survival compared with the other groups (p < 0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and monocyte chemotactic protein-1 were elevated 24 hours after CLP in aged animals compared with 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 tumor necrosis factor-alpha, IL-6, and IL-10 were higher in aged mice subjected to 1 x 30 CLP than young mice subjected to 2 x 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 of 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 with 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.
Authors: Craig M Coopersmith; Katherine C Chang; Paul E Swanson; Kevin W Tinsley; Paul E Stromberg; Timothy G Buchman; Irene E Karl; Richard S Hotchkiss Journal: Crit Care Med Date: 2002-01 Impact factor: 7.598
Authors: Isaiah R Turnbull; Joseph J Wlzorek; Dale Osborne; Richard S Hotchkiss; Craig M Coopersmith; Timothy G Buchman Journal: Shock Date: 2003-04 Impact factor: 3.454
Authors: C Oberholzer; A Oberholzer; F R Bahjat; R M Minter; C L Tannahill; A Abouhamze; D LaFace; B Hutchins; M J Clare-Salzler; L L Moldawer Journal: Proc Natl Acad Sci U S A Date: 2001-09-11 Impact factor: 11.205
Authors: Timothy P Plackett; Eric M Schilling; Douglas E Faunce; Mashkoor A Choudhry; Pamela L Witte; Elizabeth J Kovacs Journal: FASEB J Date: 2003-02-19 Impact factor: 5.191
Authors: Dina C Nacionales; Lori F Gentile; Erin Vanzant; M Cecilia Lopez; Angela Cuenca; Alex G Cuenca; Ricardo Ungaro; Yi Li; Tezcan Ozrazgat Baslanti; Azra Bihorac; Frederick A Moore; Henry V Baker; Christiaan Leeuwenburgh; Lyle L Moldawer; Philip A Efron Journal: J Immunol Date: 2013-12-13 Impact factor: 5.422
Authors: Amy C Fox; Elise R Breed; Zhe Liang; Andrew T Clark; Brendan R Zee-Cheng; Katherine C Chang; Jessica A Dominguez; Enjae Jung; W Michael Dunne; Eileen M Burd; Alton B Farris; David C Linehan; Craig M Coopersmith Journal: J Immunol Date: 2011-07-06 Impact factor: 5.422
Authors: Cynthia H Canan; Nandan S Gokhale; Bridget Carruthers; William P Lafuse; Larry S Schlesinger; Jordi B Torrelles; Joanne Turner Journal: J Leukoc Biol Date: 2014-06-16 Impact factor: 4.962
Authors: Sachin Kale; Sachin Yende; Lan Kong; Amy Perkins; John A Kellum; Anne B Newman; Abbe N Vallejo; Derek C Angus Journal: PLoS One Date: 2010-11-04 Impact factor: 3.240
Authors: Nathan J Klingensmith; Benyam P Yoseph; Zhe Liang; John D Lyons; Eileen M Burd; Lindsay M Margoles; Michael Koval; Mandy L Ford; Craig M Coopersmith Journal: Shock Date: 2017-02 Impact factor: 3.454