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 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.
Yoshimura
T
T
Pharmaceutical Division, Ogaki Municipal Hospital, Gifu, Japan.
Usami
E
E
Kurita
C
C
Watanabe
S
S
Nakao
T
T
Kobayashi
J
J
Yamazaki
F
F
Nagai
H
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D013806:Theophylline