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

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.