Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver.

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Liao J, Keiser JA, Scales WE, Kunkel SL, Kluger MJ

Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver.

Am J Physiol. 1995 Apr;268(4 Pt 2):R896-901. doi: 10.1152/ajpregu.1995.268.4.R896.

PubMed ID

7733399 [ View in PubMed

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Abstract

A bidirectional communication exists between the nervous system and the immune system. Evidence has accumulated suggesting that cytokines-immune peptides influence sympathetic neuronal survival and that cytokines can promote the secretion of catecholamines. Using an isolated perfused rat liver (IPRL) preparation, we have shown that the liver is an important source of circulating cytokines in response to lipopolysaccharide (LPS) and that corticosterone dose dependently influenced LPS-induced production of tumor necrosis factor (TNF) and interleukin-6 (IL-6). In this study, we investigated the direct effect of epinephrine (another stress hormone) on the production of TNF and IL-6 in liver. We demonstrated that epinephrine (1 microM/ml) alone did not induce TNF bioactivity but significantly increased IL-6 bioactivity from IPRL effluent. When the IPRL was infused with LPS, epinephrine significantly decreased TNF bioactivity. Epinephrine in LPS-treated livers also significantly increased IL-6 bioactivity. Both responses were totally inhibited by the beta-blocker propranolol (10 microM/ml). Anisomycin, a protein synthesis inhibitor, infused into the IPRL completely blocked the rise in TNF and IL-6 concentrations in the effluent leaving the IPRL, supporting the hypothesis that the synthesis (or release) of these cytokines was dependent on protein synthesis. We then attempted to determine whether epinephrine exerts similar effects in vitro. Using isolated Kupffer cells and hepatocytes, we found that epinephrine alone had no effect on TNF and IL-6 production in Kupffer cells and hepatocytes but significantly decreased LPS-induced TNF bioactivity and increased LPS-induced IL-6 bioactivity in Kupffer cells. Our data support the hypothesis that epinephrine can promote IL-6 secretion from IPRL.(ABSTRACT TRUNCATED AT 250 WORDS)

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Epinephrine	Tumor necrosis factor	Protein	Humans	Unknown	Antagonist Agonist	Details