Effects of formoterol and salmeterol on the production of Th1- and Th2-related chemokines by monocytes and bronchial epithelial cells

• Published in: The European respiratory journal Vol. 31; no. 6; pp. 1313 - 1321
• Main Authors: Hung, C-H, Chu, Y-T, Hua, Y-M, Hsu, S-H, Lin, C-S, Chang, H-C, Lee, M-S, Jong, Y-J
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.06.2008; Maney
• Subjects: ADAM Proteins - metabolism; Adrenergic beta-Agonists - pharmacology; Albuterol - analogs & derivatives; Albuterol - pharmacology; Biological and medical sciences; Bronchi - cytology; Bronchi - drug effects; Cell Line; Chemokine CCL17 - metabolism; Chemokine CXCL10 - metabolism; Chemokines - metabolism; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Ethanolamines - pharmacology; Formoterol Fumarate; Humans; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Pneumology; Salmeterol Xinafoate; Th1 Cells - physiology; Th2 Cells - physiology; Tumor Suppressor Proteins - metabolism; Agonist; Monocyte; bronchial epithelial cells; Bronchodilator; bronchodilators; Salmeterol; Bronchus; Th1 lymphocyte; CC chemokine; CC chemokines; Immunological investigation; β2-Adrenoreceptor agonist; T-Lymphocyte; Epithelial cell; Formoterol; Th2 lymphocyte; Macrophage; Pneumology
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00121406

It is unknown whether formoterol and salmeterol, two long-acting beta(2)-adrenoreceptor agonists, have regulatory functions in the production of T-helper cell (Th) type 2- and Th1-related chemokines by monocytes and bronchial epithelial cells. In the present study, the effects of formoterol and salmeterol on lipopolysaccharide (LPS)-induced expression of the Th2-related chemokine macrophage-derived chemokine (MDC; CCL22) and the Th1-related chemokine interferon-gamma-inducible protein (IP)-10 (CXCL10) were investigated in a monocytic cell line, THP-1, and in human primary monocytes. In addition, their effects on the expression of the Th2-related chemokine thymus- and activation-regulated chemokine (TARC; CCL17) were evaluated in an epithelial cell line, BEAS-2B. Formoterol enhanced MDC but suppressed IP-10 production in monocytes induced by LPS. Higher doses of salmeterol were required to enhance LPS-induced MDC expression in THP-1 cells. Formoterol and salmeterol could significantly suppress TARC expression in BEAS-2B cells. These effects could be reversed by a selective beta(2)-adrenoreceptor antagonist, ICI-118551. Formoterol- and LPS-induced MDC expression was inhibited by budesonide. Both long-acting beta(2)-adrenoreceptor agonists suppressed thymus- and activation-regulated chemokine expression in bronchial epithelial cells mediated via beta(2)-adrenoreceptors. Formoterol at physiological concentrations could suppress lipopolysaccharide-induced T-helper cell type 1-related chemokine (interferon-gamma-inducible protein-10) but enhance T-helper cell type 2-related chemokine (macrophage-derived chemokine) expression in human monocytes. Long-acting beta(2)-adrenoreceptor agonists may increase T-helper cell type 2-related chemokine expression in monocytes and T-helper cell type 2 recruitment and, therefore, long-acting beta(2)-adrenoreceptor agonist monotherapy may not be an appropriate therapeutic option for asthma.