Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.
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.
van der Poll
T
T
Cornell University Medical College, Department of Surgery, New York, NY 10021, USA.
Coyle
S M
SM
Barbosa
K
K
Braxton
C C
CC
Lowry
S F
SF
D000328:Adult; D004731:Endotoxins; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014115:Toxemia / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D004731:Endotoxins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004837:Epinephrine