Mouse tumor necrosis factor-α increases brain tryptophan concentrations and norepinephrine metabolism while activating the HPA axis in mice

被引:48
作者
Ando, T [1 ]
Dunn, AJ [1 ]
机构
[1] Louisiana State Univ, Med Ctr, Dept Pharmacol & Therapeut, Shreveport, LA 71130 USA
关键词
tumor necrosis factor-alpha; tryptophan; norepinephrine; serotonin; corticosterone;
D O I
10.1159/000026391
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Endotoxin (LPS) administration has been shown to activate the hypothalamo-pituitary-adrenocortical (HPA) axis and increase cerebral catecholamine and indolamine metabolism and tryptophan concentrations. LPS stimulates the secretion of tu mor necrosis factor-alpha TNF-alpha as well as interleukin-l and interleukin-6. We have investigated the role of TNF-alpha in the LPS-induced neurochemical and neuroendocrine changes. When recombinant mouse TNF-alpha (mTNF-alpha) was injected intraperitoneally (i.p.) into mice, plasma corticosterone concentrations were elevated reaching a peak at 30 min. Two hours after injection, cerebral tryptophan concentrations were also elevated in several brain regions, as well as the ratio of brain 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG)to norepinephrine (NE) in the hypothalamus. An intravenous (i.v.) injection of mTNF-alpha also increased cerebral tryptophan concentrations and MHPG/NE ratios at 2h and caused a rapid and prolonged elevation of plasma corticosterone concentrations lasting for at least 2h. We observed no significant changes in dopamine or its catabolites, or in 5-hydroxytryptamine or its major catabolite, 5-hydroxyindoleacetic acid, after either i.p, or i.v. injections. These results suggest that TNF-alpha may contribute to the HPA, neurochemical and behavioral responses to LPS and other stimulators of the immune system.
引用
收藏
页码:319 / 329
页数:11
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