Human lung and monocyte-derived macrophages differ with regard to the effects of beta(2)-adrenoceptor agonists on cytokine release

Background: beta(2)-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of beta(2)-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs. Methods: LMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF. LMs and MDMs were incubated in the absence or presence of formoterol or salmeterol prior to stimulation with LPS. The effects of formoterol were also assessed in the presence of the phosphodiesterase inhibitor roflumilast. Results: LPS-induced cytokine production was higher in LMs than in MDMs. Salmeterol and formoterol exerted an inhibitory effect on the LPS-induced production of TNF-alpha, IL-6, CCL2, CCL3, and CCL4 in MDMs. In contrast, the beta(2)-adrenoceptor agonists were devoid of any effect on LMs-even in the presence of roflumilast. The expression of beta(2)-adrenergic receptors was detected on Western blots in MDMs but not in LMs. Conclusions: Concentrations of beta(2)-adrenoceptor agonists that cause relaxation of the human bronchus can inhibit cytokine production by LPS-stimulated MDMs but not by LMs