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

J Clin Invest. 1996 Feb 1;97(3):713-9. doi: 10.1172/JCI118469.


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) 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 alpha and beta adrenergic receptors. Further, in LPS-stimulated blood, the increase on 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Endotoxins*
  • Epinephrine / pharmacology*
  • Humans
  • Infusions, Intravenous
  • Interleukin-10 / biosynthesis*
  • Male
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Toxemia / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Endotoxins
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Epinephrine