Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis

Am J Physiol Cell Physiol. 2004 Sep;287(3):C730-6. doi: 10.1152/ajpcell.00562.2003. Epub 2004 May 19.


Enhanced adrenergic stimulation and catecholamine release are important components of the pathophysiology of sepsis. Under physiological conditions, adrenergic stimulation has been shown to be a negative regulator of proinflammatory cytokine production through increasing IL-10 production. Here we have investigated if adrenergic stimulation similarly inhibits TNF-alpha and IL-6 production by splenic macrophages isolated from a polymicrobial sepsis model. Male B(6)D(2)F(1) mice were subjected to sham (S), laparotomy (Lap), and cecal ligation and puncture (CLP) under anesthesia. Splenic macrophages were isolated 72 h after the initial injury and were stimulated with endotoxin (LPS) in the presence and absence of epinephrine. Compared with S and Lap, splenic macrophages from the CLP group produced significantly less TNF-alpha and IL-6 and more IL-10 when stimulated with LPS. Macrophage cultures from CLP animals incubated with either epinephrine or IL-10 for 2 h had significantly reduced TNF-alpha and IL-6 release in response to LPS. However, similar cultures pretreated with IL-10 antibody before the addition of exogenous epinephrine failed to reverse the attenuation of LPS-stimulated cytokines. Pretreatment of macrophage cultures with beta(2)- (ICI-118551) but not beta(1)-adrenergic (atenolol) receptor antagonists reversed the epinephrine-mediated cytokine attenuation following LPS treatment. Data are also presented that demonstrate the involvement of protein kinase A activation with adrenergic agonist but not with IL-10 stimulation. Taken together, these findings suggest that adrenergic mechanisms may influence peripheral tissue macrophage inflammatory cytokine response following trauma and sepsis, independent of the effects of IL-10.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytokines / drug effects
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Disease Models, Animal
  • Endotoxins / pharmacology
  • Enzyme Activation / physiology
  • Epinephrine / metabolism*
  • Macrophage Activation / drug effects
  • Macrophage Activation / physiology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Mice
  • Sepsis / immunology
  • Sepsis / physiopathology*
  • Spleen / immunology*
  • Spleen / metabolism


  • Adrenergic Agonists
  • Adrenergic beta-Antagonists
  • Cytokines
  • Endotoxins
  • Cyclic AMP-Dependent Protein Kinases
  • Epinephrine