Epinephrine inhibits endotoxin-induced IL-1β production:: roles of tumor necrosis factor-α and IL-10

Epinephrine has been found to inhibit the production of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha and to enhance the production of anti-inflammatory cytokine interleukin (IL)-10. To determine the effect of epinephrine on IL-1 beta production, the following experiments were performed: I) blood obtained from subjects at 4-21 h after the start of a continuous infusion of epinephrine (30 ng.kg(-1).min(-1)) produced less IL-1 beta after ex vivo stimulation with lipopolysaccharide (LPS), compared with blood drawn from subjects infused with saline; 2) in whole blood in vitro, epinephrine caused a dose-dependent decrease in LPS-induced IL-1 beta production, which was likely mediated via adrenergic receptors; and 3) inhibition of TNF and enhancement of IL-10 both contributed to epinephrine-induced inhibition of IL-1 beta production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may attenuate excessive activity of proinflammatory cytokines early in the course of systemic infection.