TY - JOUR
T1 - The role of heat shock protein 70 in mediating age-dependent mortality in sepsis
AU - McConnell, Kevin W.
AU - Fox, Amy C.
AU - Clark, Andrew T.
AU - Chang, Nai Yuan Nicholas
AU - Dominguez, Jessica A.
AU - Farris, Alton B.
AU - Buchman, Timothy G.
AU - Hunt, Clayton R.
AU - Coopersmith, Craig M.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70-/- and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70-/- and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70-/- mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70-/- mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70-/- mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.
AB - Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70-/- and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70-/- and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70-/- mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70-/- mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70-/- mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.
UR - http://www.scopus.com/inward/record.url?scp=79953186909&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1003652
DO - 10.4049/jimmunol.1003652
M3 - Article
C2 - 21296977
AN - SCOPUS:79953186909
SN - 0022-1767
VL - 186
SP - 3718
EP - 3725
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -