Epinephrine inhibits tumor necrosis factor-α and potentiates interleukin 10 production during human endotoxemia

Tom Van Der Poll, Susette M. Coyle, Karen Barbosa, Carla C. Braxton, Stephen F. Lowry

Research output: Contribution to journalArticlepeer-review

Abstract

Short-term preexposure of mononuclear cells to epinephrine inhibits LPS- induced production of TNF, whereas preexposure for 24 h results in increased TNF production. To assess the effects of epinephrine infusions of varying duration on in vivo responses to LPS, the following experiments were performed: (a) Blood obtained from eight subjects at 4-24 h after the start of a 24-h infusion of epinephrine (30 ng/kg per min) produced less TNF after ex vivo stimulation with LPS compared with blood drawn before the start of the infusion, and (b) 17 healthy men who were receiving a continuous infusion of epinephrine (30 ng/kg per min) started either 3 h (EPI-3; n = 5) or 24 h (EPI-24; n = 6) before LPS injection or an infusion of normal saline (LPS; n = 6) were studied after intravenous injection of LPS (2 ng/kg, lot EC-5). EPI-3 inhibited LPS-induced in vivo TNF appearance and also increased IL-10 release (both P < 0.005 versus LPS), whereas EPI-24 only attenuated TNF secretion (P = 0.05). In separate in vitro experiments in whole blood, epinephrine increased LPS-induced IL-10 release by a combined effect on α and β adrenergic receptors. Further, in LPS-stimulated blood, the increase in IL-10 levels caused by epinephrine only marginally contributed to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection.

Original languageEnglish (US)
Pages (from-to)713-719
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number3
DOIs
StatePublished - Feb 1 1996

Keywords

  • adrenergic receptors
  • cAMP
  • cytokines
  • lipopolysaccharide
  • norepinephrine

ASJC Scopus subject areas

  • Medicine(all)

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