The effects of beta 2-adrenoceptor agonists and a corticosteroid, budesonide, on the secretion of inflammatory mediators from monocytes

Br J Pharmacol. 1992 Sep;107(1):156-60. doi: 10.1111/j.1476-5381.1992.tb14479.x.

Abstract

1. The in vitro effects of the beta 2-adrenoceptor agonists (1 x 10(-9)-10(-5) M), terbutaline, salmeterol, and formoterol, on the release of inflammatory mediators, i.e. the eicosanoids leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) and the cytokine interleukin-1 beta (IL-1 beta), were assessed in cultures of human blood monocytes. For comparison, the effects of a 5-lipoxygenase inhibitor, BW A4C (1 x 10(-9)-10(-5) M), and a corticosteroid, budesonide (1 x 10(-10)-10(-5) M) were also examined. Sotalol was used to investigate whether the actions of beta 2-agonists were mediated through beta-adrenoceptors. 2. Terbutaline, like budesonide, had no significant effect on LTB4 release, whereas BW A4C (IC50 = 2 x 10(-8) M) was a potent inhibitor. All concentrations of formoterol approximately halved the LTB4 secretion, whereas high concentrations (1 x 10(-7)-10(-5) M) only, of salmeterol, inhibited release. Only salmeterol, at high concentrations (greater than 1 x 10(-6) M), lowered the secretion of PGE2 in monocyte cultures. Formoterol and salmeterol reduced the secretion of IL-1 beta only at the highest dose (1 x 10(-5) M). In contrast, budesonide (greater than or equal to 1 x 10(-9) M) was a potent suppressant of this secretion. 3. Treatment of monocyte cultures with sotalol (1 x 10(-5) M) did not significantly antagonize the inhibitory effects of salmeterol and formoterol. These results suggest that the inhibitory action of these beta 2-agonists on the release of eicosanoids or IL-1 beta, is not mediated via beta 2-adrenoceptors.4. This study does not support a therapeutic importance of the anti-release effects of beta2-agonists since high concentrations were generally required. Furthermore, the anti-secretory action of beta2-agonists was distinct from that of corticosteroids.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / analogs & derivatives
  • Albuterol / pharmacology
  • Benzeneacetamides*
  • Budesonide
  • Cells, Cultured
  • Dinoprostone / metabolism
  • Eicosanoids / metabolism*
  • Ethanolamines / pharmacology
  • Formoterol Fumarate
  • Glucocorticoids / pharmacology
  • Humans
  • Hydroxamic Acids / pharmacology
  • Interleukin-1 / metabolism*
  • Leukotriene B4 / metabolism
  • Lipoxygenase Inhibitors / pharmacology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Pregnenediones / pharmacology*
  • Salmeterol Xinafoate
  • Terbutaline / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Benzeneacetamides
  • Eicosanoids
  • Ethanolamines
  • Glucocorticoids
  • Hydroxamic Acids
  • Interleukin-1
  • Lipoxygenase Inhibitors
  • Pregnenediones
  • N-(3-phenoxycinnamyl)acetohydroxamic acid
  • Leukotriene B4
  • Budesonide
  • Salmeterol Xinafoate
  • Dinoprostone
  • Terbutaline
  • Albuterol
  • Formoterol Fumarate