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

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.