Effect of theophylline on the production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-8 by human peripheral blood mononuclear cells. 1995

T Yoshimura, and E Usami, and C Kurita, and S Watanabe, and T Nakao, and J Kobayashi, and F Yamazaki, and H Nagai
Pharmaceutical Division, Ogaki Municipal Hospital, Gifu, Japan.

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.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010835 Phytohemagglutinins Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture. Kidney Bean Lectin,Kidney Bean Lectins,Lectins, Kidney Bean,Phaseolus vulgaris Lectin,Phaseolus vulgaris Lectins,Phytohemagglutinin,Hemagglutinins, Plant,Lectin, Kidney Bean,Lectin, Phaseolus vulgaris,Lectins, Phaseolus vulgaris,Plant Hemagglutinins
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000894 Anti-Inflammatory Agents, Non-Steroidal Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D013806 Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP. 1,3-Dimethylxanthine,3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione,Accurbron,Aerobin,Aerolate,Afonilum Retard,Aquaphyllin,Armophylline,Bronchoparat,Bronkodyl,Constant-T,Elixophyllin,Euphylong,Glycine Theophyllinate,Lodrane,Monospan,Nuelin,Nuelin S.A.,Quibron T-SR,Slo-Phyllin,Somophyllin-T,Sustaire,Synophylate,Theo Von Ct,Theo-24,Theo-Dur,Theobid,Theocin,Theoconfin Continuous,Theodur,Theolair,Theolix,Theon,Theonite,Theopek,Theophylline Anhydrous,Theophylline Sodium Glycinate,Theospan,Theostat,Theovent,Uniphyl,Uniphyllin,Uniphylline,1,3 Dimethylxanthine,Anhydrous, Theophylline,Constant T,ConstantT,Ct, Theo Von,Glycinate, Theophylline Sodium,Quibron T SR,Quibron TSR,Slo Phyllin,SloPhyllin,Sodium Glycinate, Theophylline,Somophyllin T,SomophyllinT,Theo 24,Theo Dur,Theo24,Theophyllinate, Glycine,Von Ct, Theo

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