Salmeterol inhibits interferon-gamma and interleukin-4 production by human peripheral blood mononuclear cells

T-lymphocytes play an important role in allergic asthma. In the present study, the effect of beta(2)-adrenoceptor agonists was examined on proliferation, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production by human peripheral blood mononuclear cells (PBMC). The proliferation after 24 h phytohaemagglutinin (PHA) activation was significantly inhibited at high concentrations of salmeterol, isoprenaline and salbutamol (> or = 10(-6) M). A U-shaped concentration response curve was observed for the effect of all agonists on IL-4 production 24 h after PHA activation. Maximal inhibition occurred at 10(-9) M and amounted to 71% (P < 0.02), 38% (P < 0.01) and 49% (P < 0.01) for salmeterol, isoprenaline and salbutamol, respectively. In contrast, no significant effect of salmeterol (10(-11)-10(-5) M) on IL-4 production could be detected after 96 h. A biphasic concentration response curve was observed for the inhibitory activity of all beta-adrenoceptor agonists on IFN-gamma production by PBMC 24 h after PHA activation. The first phase reached a plateau at 10(-9) M and the inhibition amounted to 50% (P < 0.05), 33% (P < 0.01) and 44% (P < 0.05) for salmeterol, isoprenaline and salbutamol, respectively. At higher concentrations of the three beta-adrenoceptor agonists the inhibition was increased up to 80% (P < 0.05), 60% (P < 0.05) and 58% (P < 0.01), respectively. Similar to the results obtained after 24 h, IFN-gamma production after 96 h was biphasically inhibited by salmeterol, and this inhibition (60%) was significantly at 10(-5) M. Together, the present data provide clear evidence for concentration-dependent effects of beta-adrenoceptor agonists on the IL-4 and IFN-gamma production by human PBMC. These results suggest that beta-agonists, at low concentrations, predominantly inhibit IL-4 production and may therefore act as anti-inflammatory drugs in allergic asthma.