An overwhelming amount of evidence suggests that the elderly are less able to survive burn injury than are young healthy individuals. Since burn victims of all ages often succumb to secondary infectious complications rather than the primary injury, and the integrity of the immune system is diminishes with age, it is likely that aged individuals are predisposed to a poor outcome by virtue of their weak immune system. Elevated production of macrophage-derived proinflammatory mediators, interleukin-6 (IL-6) and prostaglandin E2 (PGE2), is thought to trigger post injury immunosuppression in young adults. Since healthy aged individuals produce high circulating levels of these mediators, the combination of the age-dependent and burn-induced elevation in the production of these mediators could further suppress immune responses and contribute to the rapid demise of aged burn patients. Preliminary data reveal that in the absence of injury, aged mice exhibit weaker cell mediated immune responses and greater production of IL-6 and PGE2 than young adult mice. Furthermore, after injury, aged mice 1) are less likely to survive, 2) cannot mount immune responses, and 3) have significantly elevated circulating levels of IL-6 than thermally injured young mice. Furthermore, administration of anti-IL-6 Ab after injury to aged mice results in marked recovery in these responses to the levels observed in sham injured aged mice. Finally, additional preliminary studies demonstrate that (young adult) IL-6 knockout mice are not immunosuppressed after burn injury. From these pieces of evidence, we hypothesize that aged mice are less able to tolerate burn trauma than are young adult mice because of the overproduction of macrophage-derived mediators, IL-6 and PGE2, which, in turn, suppress cell mediated immune responses. To address this, we will a) examine cell mediated immune responses in aged versus young adult mice following thermal injury, b) monitor the production of key proinflammatory mediators (IL-6 and PGE2) in peripheral blood and in supernatants from cultured macrophage, c) determine whether adoptive transfer of leukocytes from aged mice suppresses cell mediated immune responses of young mice, and d) determine whether aberrant of these mediators are critically responsible for decreased immune responses by blocking the production of the mediator, the response to that mediator, and performing parallel studies in knockout mice. Such studies will yield valuable information about the mechanisms by which aging effects survival in the burned individual and may suggests that age-specific therapies should be considered for treatment of all patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG018859-04
Application #
6702243
Study Section
Geriatrics and Rehabilitation Medicine (GRM)
Program Officer
Fuldner, Rebecca A
Project Start
2001-02-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
4
Fiscal Year
2004
Total Cost
$259,000
Indirect Cost
Name
Loyola University Chicago
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
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