Asthma, adenosine, mast cells and theophylline.
Many clinical trials have suggested that theophylline has anti-inflammatory properties in the treatment of bronchial asthma. Proposed mechanisms of theophylline inhibition include phosphodiesterase inhibition, an adenosine receptor antagonist, the increase of circulating adrenaline, mediator antagonist and inhibition of calcium ion influx. Further to these observations we report on the inhibition by theophylline of NF-kappaB, a key transcription factor found in human purified mast cells, which plays a role in the transcription of TNF alpha, GM-CSF, and IL-8 within this cell. The suppression of NF-kappaB activation, indicates that theophylline, in addition to its bronchodilator activities, has the potential for anti-inflammatory activity.
Immunopharmacology Group, Southampton General Hospital, UK.
W R
WR
Coward
H
H
Sagara
M K
MK
Church
D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors; D013806:Theophylline / Q000494:pharmacology / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D013806:Theophylline; D000241:Adenosine