EPINEPHRINE INHIBITS TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES INTERLEUKIN-10 PRODUCTION DURING HUMAN ENDOTOXEMIA

Short-term preexposure of mononuclear cells to epinephrine inhibits LP S-induced production of TNF, whereas preexposure for 24 h results in i ncreased TNF production, To assess the effects of epinephrine infusion s of varying duration on in vivo responses to LPS, the following exper iments 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 bl ood 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 a fter 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 secreti on (P = 0.05). In separate in vitro experiments in whole blood, epinep hrine increased LPS-induced IL-10 release by a combined effect on alph a and beta adrenergic receptors. Further, in LPS-stimulated blood, the increase in IL-10 levels caused by epinephrine only marginally contri buted to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatme nt, may have a net antiinflammatory effect on the cytokine network ear ly in the course of systemic infection.