Exogenous and endogenous catecholamines inhibit the production of macrophage inflammatory protein (MIP) 1 alpha via a beta adrenoceptor mediated mechanism

Br J Pharmacol. 1998 Nov;125(6):1297-303. doi: 10.1038/sj.bjp.0702179.


Noradrenaline (NA) and adrenaline (Ad) are modulators of cytokine production. Here we investigated the role of these neurotransmitters in the regulation of macrophage inflammatory protein (MIP)-1alpha expression. Pretreatment of RAW 264.7 macrophages with NA or Ad decreased, in a concentration-dependent manner (1 nM-100 microM), MIP-1alpha release induced by bacterial lipopolysaccharide (LPS 10 ng ml(-1) LPS). The effect of NA was reversed by the selective beta-adrenoceptor antagonist propranolol (10 microM), but not by the alpha-adrenoceptor antagonist phentolamine (10 microM). In the concentration range of 10 nM-10 microM, isoproterenol, a beta-adrenoceptor agonist, but not phenylephrine (a selective alpha1-adrenoceptor agonist) or UK-14304 (a selective alpha2-adrenoceptor agonist) mimicked the inhibitory effects of catecholamines on MIP-1alpha production. Increases in intracellular cyclic adenosine monophosphate, elicited either by the selective type IV phosphodiesterase inhibitor rolipram (0.1 - 10 microM), or by prostaglandin E2, (10 nM-10 microM) decreased MIP-1alpha release, suggesting that increased cyclic AMP may contribute to the suppression of MIP-1alpha release by beta-adrenoceptor stimulation. Northern blot analysis demonstrated that NA (100 nM-10 microM), Ad, isoproterenol, as well as rolipram (100 nM-10 microM) decreased LPS-induced MIP-1alpha mRNA accumulation. NA and Ad (1-100 microM) also decreased MIP-1alpha production in thioglycollate-elicited murine peritoneal macrophages. Pretreatment of mice with either isoproterenol (10 mg kg(-1), i.p.) or rolipram (25 mg kg(-1), i.p.) decreased LPS-induced plasma levels of MIP-1alpha, while propranolol (10 mg kg(-1), i.p.) augmented the production of this chemokine, confirming the role of a beta-adrenoceptor mediated endogenous catecholamine action in the regulation of MIP-1alpha production in vivo. Thus, based on our data we conclude that catecholamines are important endogenous regulators of MIP-1alpha expression in inflammation.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Antibody Formation
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Cyclic AMP / metabolism
  • Cyclic AMP / physiology
  • Epinephrine / pharmacology*
  • Epinephrine / physiology*
  • Isoproterenol / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophage Inflammatory Proteins / biosynthesis*
  • Macrophage Inflammatory Proteins / blood
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Norepinephrine / pharmacology*
  • Norepinephrine / physiology*
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology
  • Thioglycolates / pharmacology


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Chemokine CCL3
  • Chemokine CCL4
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Receptors, Adrenergic, beta
  • Thioglycolates
  • Cyclic AMP
  • Isoproterenol
  • Norepinephrine
  • Epinephrine