EFFECTS OF BETA(2)-AGONISTS AND BUDESONIDE ON INTERLEUKIN-1-BETA AND LEUKOTRIENE B-4 SECRETION - STUDIES OF HUMAN MONOCYTES AND ALVEOLAR MACROPHAGES

The aims of the present study were to determine whether beta(2)-agonis ts (short- and long-acting) and a glucocorticoid (budesonide) influenc e the secretion of a pro-inflammatory cytokine (interleukin-1, [IL-1]) and a granulocyte attractant (leukotriene B-4 [LTB4]) and to compare these effects on blood monocyte and alveolar macrophages. Alveolar mac rophages (obtained by bronchoalveolar lavage) and blood monocytes from 26 healthy nonsmokers were stimulated with lipopolysaccharide or huma n serum opsonized zymosan. The influence of four beta(2)-agonists (sal butamol, terbutaline, formoterol, and salmeterol) and a corticosteroid (budesonide) on the release of interleukin-1 beta (IL-1 beta) and LTB 4 was studied in a dose-response manner (10(-8)-10(-5) mol/L for beta( 2)-agonists and 10(-10)-10(-6) mol/L for budesonide). The stimulated I L-1 beta secretion was significantly greater in blood monocytes than i n alveolar macrophages (p < 0.05), but alveolar macrophages were much more capable of secreting LTB4 than were blood monocytes (p < 0.001). Budesonide significantly inhibited the release of IL-1 beta from blood monocytes (p < 0.001), but no such effect was observed in alveolar ma crophages. Budesonide did not influence the release of LTB4 in either cell type. The beta(2)-agonists neither influenced the LTB4 nor the IL -beta secretion in either cell type with the exception of formoterol, which stimulated IL-1 beta secretion at the highest concentration (10( -5) mol/L, p<0.05). In conclusion, beta(2)-agonists exhibited only min or effects on IL-1 beta secretion from blood monocytes and no effect o n LTB4-secretion from either cell type, and budesonide effectively inh ibited the IL-1 beta release in blood monocytes, but not in alveolar m acrophages. Thus, induced secretion of LTB4 and IL-1 beta, and the sen sitivity to corticosteroids with regard to IL-1 beta secretion, change during the transformation from blood monocytes to alveolar macrophage s.