Salmeterol inhibits the allergen-induced mononuclear cell proliferation and downregulates GM-CSF release and HLA-DR expression by monocytes

Pulm Pharmacol Ther. 1997;10(1):43-9. doi: 10.1006/pupt.1997.0073.

Abstract

beta 2-adrenoceptor agonists are known to attenuate several functions of human mononuclear cells in response to activation. Since monocytes and lymphocytes play a major pathogenetic role in allergic asthma, this study was designed to evaluate the hypothesis that salmeterol, a beta 2-adrenoceptor agonist with a long duration of action, could inhibit in vitro the allergen-induced activation of blood mononuclear cells (BMCs). BMCs were collected from subjects sensitized to Dermatophagoides pteronyssinus (Der p) and incubated with a purified Der p allergen extract to evaluate the ability of salmeterol to downregulate; (a) BMC proliferation; (b) IL-2 receptors (r) and HLA-DR surface antigen (ag) expression; (c) cytokine release. Der p induced a significant BMC proliferation (P < 0.01), associated with increased expression of HLA-DRag and IL-2r (P < 0.05) and with enhanced release of IL-2, GM-CSF, IL-1 beta, TNF-alpha and IFN-gamma (P < 0.01, each comparison). Salmeterol (10(-8)-10(-6) M) significantly inhibited, in a dose dependent manner, the Der p-induced BMC proliferation, reducing (at 10(-7) M) HLA-DRag expression on monocytes and GM-CSF release (P < 0.05, each comparison). These data demonstrate that beta 2-adrenoceptor-mediated suppression of allergen-induced BMC activation is associated with inhibition of cytokine release and of surface molecule expression, which are involved in the interaction between T-lymphocytes and antigen-presenting cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Adult
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacology
  • Allergens / pharmacology*
  • Bronchodilator Agents / pharmacology*
  • Cell Division / drug effects
  • Cytokines / metabolism
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • HLA-DR Antigens / metabolism*
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Receptors, Interleukin-2
  • Salmeterol Xinafoate

Substances

  • Adrenergic beta-Agonists
  • Allergens
  • Bronchodilator Agents
  • Cytokines
  • HLA-DR Antigens
  • Receptors, Interleukin-2
  • Salmeterol Xinafoate
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Albuterol