Stimulation of beta-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice

J Neuroimmunol. 1998 Aug 1;88(1-2):57-61. doi: 10.1016/s0165-5728(98)00073-3.


Stimulation of beta-adrenoceptors has been shown to regulate the production of various inflammatory mediators. In the present study, we investigated in mice whether ligation of beta-adrenoceptors, modulates lipopolysaccharide (LPS)-induced plasma levels of interleukin (IL)-12, interferon-gamma (IFN-gamma), and IL-10. In BALB/c mice, isoproterenol (1-10 mg kg(-1) , i.p.), a selective agonist of beta-adrenoceptors and also dexamethasone (10 mg kg(-1), i.p.) pretreatment 30 min before the administration of LPS suppressed plasma IL-12 (p40 and p70) concentrations as determined at various time points after the LPS challenge. The inhibition of IL-12 release by isoproterenol was prevented by the beta-adrenoceptor antagonist propranolol confirming the involvement of beta-adrenoceptors in the effect of isoproterenol. Furthermore, pretreatment of the animals with propranolol alone enhanced LPS-induced plasma IL-12, suggesting that endogenous catecholamines inhibit IL-12 production via the beta-adrenoceptors. In IL-10 deficient C57BL/6 IL-10(-/-) mice, plasma levels of IL-12 and IFN-gamma were significantly higher than in their counterparts, with more than 70-fold increase in IL-12. Furthermore, while augmenting the IL-10 response in C57BL/6 IL-10(+/+), isoproterenol inhibited the production of IL-12 in both the C57BL/6 IL-10(+/+) and C57BL/6 IL-10(-/-) mice, suggesting that the inhibition of IL-12 production by this compound is independent of the increased release of IL-10. Our results demonstrate, for the first time, that stimulation of beta-adrenoceptors by isoproterenol or endogenous catecholamines suppresses IL-12 production in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Endotoxins / pharmacology*
  • Interleukin-10 / deficiency*
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / blood
  • Isoproterenol / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Adrenergic, beta / physiology*
  • Reference Values


  • Adrenergic beta-Agonists
  • Endotoxins
  • Receptors, Adrenergic, beta
  • Interleukin-10
  • Interleukin-12
  • Isoproterenol