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 presen t study, the effect of beta(2)- adrenoceptor agonists was examined on proliferation, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) p roduction by human peripheral blood mononuclear cells (PBMC). The prol iferation after 24 h phytohaemagglutinin (PHA) activation was signific antly inhibited at high concentrations of salmeterol, isoprenaline and salbutamol (greater than or equal to 10(-6) M). A U-shaped concentrat ion 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) f or salmeterol, isoprenaline and salbutamol, respectively. In contrast, no significant effect of salmeterol (10(-11)-10(-5) M) on IL-4 produc tion could be detected after 95 h. A biphasic concentration response c urve was observed for the inhibitory activity of all beta-adrenoceptor agonists on IFN-gamma production by PBMC 24 h after PHA activation. T he first phase reached a plateau at 10(-9) M and the inhibition amount ed to 50% (P<0.05), 33% (P<0.01) and 44% (P<0.05) for salmeterol, isop renaline and salbutamol, respectively. At higher concentrations of the three beta-adrenoceptor agonists the inhibition was increased up to 8 0% (P<0.05), 60% (P<0.05) and 58% (P<0.01), respectively. Similar to t he results obtained after 24 h, IFN-gamma production after 96 h was bi phasically inhibited by salmeterol, and this inhibition (60%) was sign ificant 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 allerg ic asthma.