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



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



Biological & Pharmaceutical Bulletin 18(10): 1405-1408



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 gtoreq 50 mu-g/ml, theophylline suppressed the proliferative activity of PBMC stimulated with phytohemagglutinin (p lt 0.05). IL-1-beta production showed 23% suppression by 10 mu-g/ml theophylline (p lt 0.05), while the suppression was 26% at 25 mu-g/ml (p lt 0.05), 30% at 50 mu-g/ml (p lt 0.05), and 33% at 100 mu-g/ml (p lt 0.05). TNF-alpha production was suppressed in a dose-dependent manner by theophylline, being decreased by 24% at 10 mu-g/ml (p lt 0.05), by 29% at 25 mu-g/ml (p lt 0.05), by 41% at 50 mu-g/ml (p lt 0.01), and by 54% at 100 mu-g/ml (p lt 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 mu-g/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.

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Accession: 008549873

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PMID: 8593446

DOI: 10.1248/bpb.18.1405


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