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

Abstract

T-lymphocytes play an important role in allergic asthma. In the present study, the effect of β 2 adrenoceptor agonists was examined on proliferation, interleukin-4 (IL-4) and interferon-γ (IFN-γ) 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 (≥10 −6M). 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 −9M 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 β-adrenoceptor agonists on IFN-γ 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 β-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-γ production after 96 h was biphasically inhibited by salmeterol, and this inhibition (60%) was significant at 10 −5 M. Together, the present data provide clear evidence for concentration-dependent effects of β-adrenoceptor agonists on the IL-4 and IFN-γ production by human PBMC. These results suggest that β-agonists, at low concentrations, predominantly inhibit IL-4 production and may therefore act as anti-inflammatory drugs in allergic asthma.