| Autor: |
Kalehua, A. N., Taub, D. D., Baskar, P. V., Hengemihle, J., Muñoz, J., Trambadia, M., Speer, D.L., De Simoni, M.-G., Ingram, D.K., Muñoz, J |
| Předmět: |
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| Zdroj: |
Gerontology; 2000, Vol. 46 Issue 3, p115-128, 14p, 2 Black and White Photographs, 1 Chart, 4 Graphs |
| Abstrakt: |
Background: Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans.Objective: We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice.Methods: Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1beta, IL-6, IL-12, and TNF-alpha were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices.Results: Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-alpha. AntiTNF-alpha- and IL-6-immunoreactive cells possessed macrophagelike morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-alpha after LPS administration compared to C3H/HeN mice.Conclusion: These results suggest that the age-related increases in TNF-alpha production and mortality following the intracerebroventricular administration of LPS may be due to an increased endotoxin hypersensitivity of brain microglia/macrophages within aged animals. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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