Salmeterol inhibits the allergen-induced mononuclear cell proliferation and downregulates GM-CSF release and HLA-DR expression by monocytes.
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.
Oddera
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S
Divisione di Pneumologia, Istituto G. Gaslini, Genova, Italy.
Silvestri
M
M
Scarso
L
L
Testi
R
R
Rossi
G A
GA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000485:Allergens / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015375:Receptors, Interleukin-2; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000485:Allergens; D001993:Bronchodilator Agents; D016207:Cytokines; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D000068299:Salmeterol Xinafoate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000420:Albuterol