TY - JOUR
T1 - Aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-alpha levels following intracerebroventricular injection of lipopolysaccharide
AU - Kalehua, A.N.
AU - Taub, D.D.
AU - Baskar, P.V.
AU - Hengemihle, J.
AU - Munoz, James R.
AU - Trambadia, M.
AU - Speer, D.L.
AU - DeSimoni, M.G.
AU - Ingram, D.K.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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.
AB - 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.
UR - https://nsuworks.nova.edu/cps_facarticles/1154
M3 - Article
SN - 0304-324X
VL - 46
JO - Gerontology
JF - Gerontology
ER -