β2-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 β2-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 tag) 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-1β, TNF-α and IFN-γ (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 β2-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.
- Interleukin-2 receptor (IL-2r)
- MHC class II molecules
- Mononuclear cells
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine