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Abstracts: Aging and Shock


Kovacs, E.J.; Plackett, T.P.*; Ramirez, L.*; Gomez, C.R.*

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In the absence of injury, the elderly exhibit a heightened basal inflammatory state referred to as "inflamm-aging." This hyperinflammatory state may predispose this population to a poor prognosis after injury or infection, relative to young adults, due to excessive tissue damage and/or suppression of immune responses. In our ongoing studies, we compared inflammatory and immune responses in young (2-4 month old) and aged (18-22 month old) BALB/C mice. Even in the absence of injury, aged animals exhibit depressed cell-mediated immune responses, including delayed type hypersensitivity and mitogen-induced splenocyte proliferation, and have higher serum levels of interleukin-6 (IL-6) when compared to young adults. Additionally, after sustaining a 15% total body surface area burn injury, aged mice have higher mortality than young. Since estrogen can act as an anti-inflammatory agent, we gave aged mice estrogen at a dose designed to elevate circulating estrogen levels to 30 pg/ml (proestrus levels in the mouse) or placebo hormone replacement. Without exogenous estrogen, we found a 4-fold increase in the serum IL-6 in aged burn-injured mice relative to aged sham-injured mice (p<0.05). This level of cytokine was reduced by 50% in aged burn-injured mice given estrogen. Additionally, after injury, in placebo treated aged animals there was a >75% suppression in the DTH response, relative to placebo-treated sham-injured aged mice (p<0.05). In contrast, estrogen treatment yielded a partial recovery in the DTH response (p<0.05). Finally, in aged mice, estrogen improved post-burn survival from 42% (in the absence of estrogen) to 70% in aged burn injured mice. These studies reveal marked differences in the responses of aged mice to burn injury and suggest that age-specific therapies should be considered for the treatment of all burn patients. (This work was supported by NIH AG18859, NIH AG18859-S1, and the Dr. Ralph and Marion C. Falk Medical Research Trust.)

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