AGE-ASSOCIATED DIFFERENCES IN TNF-ALPHA AND NITRIC-OXIDE PRODUCTION IN ENDOTOXIC MICE

Citation
Bb. Chorinchath et al., AGE-ASSOCIATED DIFFERENCES IN TNF-ALPHA AND NITRIC-OXIDE PRODUCTION IN ENDOTOXIC MICE, The Journal of immunology, 156(4), 1996, pp. 1525-1530
Citations number
31
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
00221767 → ACNP
Volume
156
Issue
4
Year of publication
1996
Pages
1525 - 1530
Database
ISI
SICI code
0022-1767(1996)156:4<1525:ADITAN>2.0.ZU;2-6
Abstract
Gram-negative bacterial infection is a common cause of septic shock in the older population in the U.S. We employed an experimental model of sepsis to study the cause of increased lethality due to LPS in older animals. Three ages of male B6JC3J/Nia mice, young (2 mo old), mature (12 mo old), and senescent (24 mo old), were treated with bacterial LP S, and the older mice were found to be 10 times more sensitive to LPS lethality. Increased sensitivity to LPS in senescent mice correlated w ith significantly elevated plasma TNF-alpha and nitric oxide levels. A bs to TNF-alpha afforded aged animals passive protection against a sup ralethal dose of LPS, establishing a central role for TNF in the incre ased sensitivity to LPS seen in the aged animals. Other cytokines, suc h as IL-1 and IFN-gamma, appeared secondary to TNF and nitric oxide in the age-associated sensitivity to LPS. Plasma corticosterone levels w ere increased by LPS at a time when maximal levels of plasma TNF-alpha were observed in both age groups, although the kinetics of hormone pr oduction and the magnitude of TNF-alpha release varied among the age g roups. Exogenously administered dexamethasone protected senescent anim als given a high dose of LPS, by decreasing cytokine levels. The incre ased sensitivity to LPS observed in aged animals, therefore, seems to be due to excessive TNF and nitric oxide production, resulting from pe rturbed endogenous hormonal control of cytokine production.