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Asthma, adenosine, mast cells and theophylline
W R Coward1, H Sagara, M K Church
1Immunopharmacology Group, Southampton General Hospital, UK.
Summary
Theophylline demonstrates anti-inflammatory effects in asthma by inhibiting NF-kappaB, a key factor in inflammatory gene transcription. This finding supports its potential beyond bronchodilation for managing asthma inflammation.
Area of Science:
- Immunology
- Pharmacology
- Respiratory Medicine
Background:
- Theophylline is recognized for potential anti-inflammatory properties in bronchial asthma treatment.
- Existing proposed mechanisms include phosphodiesterase inhibition and adenosine receptor antagonism.
Purpose of the Study:
- To investigate the effect of theophylline on NF-kappaB activation in human mast cells.
- To explore the role of theophylline in regulating inflammatory gene transcription.
Main Methods:
- Human purified mast cells were utilized.
- Theophylline's effect on NF-kappaB activation was assessed.
- The impact on transcription factors like TNF alpha, GM-CSF, and IL-8 was examined.
Main Results:
- Theophylline was found to inhibit NF-kappaB activation in human mast cells.
- This inhibition affects the transcription of key inflammatory mediators such as TNF alpha, GM-CSF, and IL-8.
Conclusions:
- Theophylline suppresses NF-kappaB activation, a crucial step in inflammatory responses.
- These findings suggest theophylline possesses anti-inflammatory potential in asthma, complementing its bronchodilator effects.