Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12

J Clin Invest. 1997 Sep 15;100(6):1513-9. doi: 10.1172/JCI119674.


Interleukin 12 (IL-12) plays a central role in the immune system by skewing the immune response towards T helper 1 (Th1) type responses which are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta2-agonists inhibit IL-12 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 production is selective, as other cytokines produced by monocytes are unaffected. IL-12 inhibition is dependent on beta2-adrenoceptor stimulation and correlates with increased levels of intracellular cAMP. In conjunction with their ability to suppress IL-12 production, when beta2-agonists are added at priming of neonatal T lymphocytes, they inhibit the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therapeutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. These findings provide new insight into the immunological consequences of the clinical use of beta2-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists*
  • Adrenergic beta-2 Receptor Antagonists
  • Adult
  • Albuterol / pharmacology
  • Bucladesine / pharmacology
  • Cell Differentiation / drug effects
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Oxprenolol / pharmacology
  • RNA, Messenger / analysis
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism*
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism


  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-2 Receptor Antagonists
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Colforsin
  • Oxprenolol
  • Bucladesine
  • Interferon-gamma
  • Cyclic AMP
  • Albuterol