Regulation of noradrenergic function by inflammatory cytokines and depolarization

Wei Li, David Knowlton, William R. Woodward, Beth A. Habecker

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Although the sympathetic neurons innervating the heart are exposed to the inflammatory cytokines cardiotrophin-1 (CT-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) after myocardial infarction, the effects of these cytokines on noradrenergic function are not well understood. We used cultured sympathetic neurons to investigate the effects of these cytokines on catecholamine content, the tyrosine hydroxylase co-factor, tetrahydrobiopterin (BH4), and norepinephrine (NE) uptake. CT-1, but not IL-6 or TNFα, suppressed NE uptake and catecholamines in these neurons, whereas CT-1 and, to a lesser extent, IL-6 decreased BH4 content. CT-1 exerted these effects by decreasing tyrosine hydroxylase, GTP cyclohydrolase (GCH) and NE transporter mRNAs, while IL-6 lowered only GCH mRNA. The neurons innervating the heart are also activated by the central nervous system after myocardial infarction. We examined the combined effect of depolarization and cytokines on noradrenergic function. In CT-1-treated cells, depolarization caused a small increase in BH4 and NE uptake, and a large increase in catecholamines. These changes were accompanied by increased TH, GCH and NE transporter mRNAs. CT-1 and depolarization regulate expression of noradrenergic properties in an opposing manner, and the combined treatment results in elevated cellular catecholamines and decreased NE uptake relative to control cells.

Original languageEnglish (US)
Pages (from-to)774-783
Number of pages10
JournalJournal of neurochemistry
Issue number3
StatePublished - Aug 2003


  • Cardiotrophin-1
  • Interleukin-6
  • Norepinephrine uptake
  • Sympathetic neuron
  • Tetrahydrobiopterin
  • Tumor necrosis factor alpha

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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