EFFECT OF THEOPHYLLINE ON THE PRODUCTION OF INTERLEUKIN-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA, AND INTERLEUKIN-8 BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Theophylline is a mild bronchodilator and has significant extrapulmona ry 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 interle ukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin 8 (IL-8) when PBMC mere stimulated with lipopolysaccharide (LPS) or recombinant human IL-1 beta (rhIL-1 beta). At concentrations greater than or equal to 50 mu g/ml, theophylline suppressed the prol iferative activitiy of PBMC stimulated with phytohemagglutinin (p < 0. 05). IL-1 beta production showed 23% suppression by 10 mu g/ml theophy lline (p < 0.05), while the suppression was 26% at 25 mu g/ml (p<0.05) , 30% at 50 mu g/ml (p<0.05), and 33% at 100 mu g/ml (p<0.05). TNF-alp ha production was suppressed in a dose-dependent manner by theophyllin e, being decreased by 24% at 10 mu g/ml (p<0.05), by 29% at 25 mu g/ml (p<0.05), by 41% at 50 mu g/ml (p<0.01), and by 54% at 100 mu g/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 co ncentrations of 1-100 units/ml, and theophylline (particularly at conc entrations of 50 and 100 mu g/ml), increased IL-8 production in the pr esence of rhIL-1 beta. Suppression of the production of IL-1 beta and TNF-alpha by therapeutic levels of theophylline suggested that this dr ug might have anti-inflammatory and immunosuppressive effects.