Effect of theophylline on the production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-8 by human peripheral blood mononuclear cells

Abstract

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-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin 8 (IL-8) when PBMC were stimulated with lipopolysaccharide (LPS) or recombinant human IL-1 beta (rhIL-1 beta). At concentrations > or = 50 micrograms/ml, theophylline suppressed the proliferative activity of PBMC stimulated with phytohemagglutinin (p < 0.05). IL-1 beta production showed 23% suppression by 10 micrograms/ml theophylline (p < 0.05), while the suppression was 26% at 25 micrograms/ml (p < 0.05), 30% at 50 micrograms/ml (p < 0.05), and 33% at 100 micrograms/ml (p < 0.05). TNF-alpha production was suppressed in a dose-dependent manner by theophylline, being decreased by 24% at 10 micrograms/ml (p < 0.05), by 29% at 25 micrograms/ml (p < 0.05), by 41% at 50 micrograms/ml (p < 0.01), and by 54% at 100 micrograms/ml (p < 0.01). IL-8 production, in contrast, was not affected by theophylline. rhIL-1 beta induced IL-8 production in a dose-dependent manner at concentrations of 1-100 units/ml, and theophylline (particularly at concentrations of 50 and 100 micrograms/ml), increased IL-8 production in the presence of rhIL-1 beta. Suppression of the production of IL-1 beta and TNF-alpha by therapeutic levels of theophylline suggested that this drug might have anti-inflammatory and immunosuppressive effects.