Effect of Theophylline on the Production of Interleukin-1β, Tumor Necrosis Factor-α, and Interleukin-8 by Human Peripheral Blood Mononuclear Cells

抄録

Theophylline is a mild bronchodilator and has significant extrapulmonary effects, but it may also have some anti-inflammatory properties. We investigated the immunological effects of theophylline on peripheral blood mononuclear cells (PBMC), by examining the production of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 8 (IL-8) when PBMC were stimulated with lipopolysaccharide (LPS) or recombinant human IL-1β (rhIL-1β). At concentrations&lnE;50μg/ml, theophylline suppressed the proliferative activitiy of PBMC stimulated with phytohemagglutinin (p<0.05). IL-1β production showed 23% suppression by 10μg/ml theophylline (p<0.05), while the suppression was 26% at 25μg/ml (p<0.05), 30% at 50μg/ml (p<0.05), and 33% at 100μg/ml (p<0.05). TNF-α production was suppressed in a dose-dependent manner by theophylline, being decreased by 24% at 10μg/ml (p<0.05), by 29% at 25μg/ml (p<0.05), by 41% at 50μg/ml (p<0.01), and by 54% at 100μg/ml (p<0.01). IL-8 production, in contrast, was not affected by theophylline. rhIL-1β induced IL-8 production in a dose-dependent manner at concentrations of 1-100 units/ml, and theophylline (particularly at concentrations of 50 and 100μg/ml), increased IL-8 production in the presence of rhIL-1β. Suppression of the production of IL-1β and TNF-α by therapeutic levels of theophylline suggested that this drug might have anti-inflammatory and immunosuppressive effects.