[Theophylline, a new look to an old drug].
OBJECTIVE
To emphasize the safety and efficacy of theophylline in chronic inflammatory respiratory diseases. To mention its immunomodulatory effects.


METHODS
PubMed search using the keywords: theophylline, histone deacetylase, antiinflammatory, asthma, chronic obstructive pulmonary disease (COPD), corticoresistance.


RESULTS
Theophylline is a methylxantine, that inhibits phosphodiesterase (PDE), induces histone deacetylase and antagonizes adenosine. Its main effect is to relax airway smooth muscle. The immunomodulatory effects of theophylline are obtained at low plasma concentrations (less than 10 mg/L). The combination of inhaled corticoesteroids and theophylline exerts a synergistic antiinflammatory effect that improves asthma control and reduces COPD exacerbations. Histones are a group of transcriptional cofactors involved in chromatin remodeling. Histone deacetylases (HDACs) suppress inflammatory gene expression. In patients with COPD and severe asthma there is a reduction in HDAC-2 secondary to the increased oxidative and nitrative stress. HDAC-2 is required by corticosteroids to switch off activated inflammatory genes, then its reduction favors corticosteroid resistance. Theophylline via HDAC-2 induction and PDE inhibition, suppresses inflammatory gene expression, and inhibits free oxygen radicals production.


CONCLUSIONS
Theophylline at low plasma concentrations exerts antiinflammatory effects, restoring corticosteroid sensitivity in COPD and severe asthma.
Medica alergóloga, Hospital Angeles Mocel, México, DF. blancamorfin@hotmail.com
Blanca María
BM
Morfín Maciel
Blanca María
BM
Castillo Morfín
D000305:Adrenal Cortex Hormones / Q000493:pharmacokinetics / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D020013:Calcium Signaling / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005544:Forecasting; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D008297:Male; D009132:Muscles / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011448:Prostaglandin Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D058915:Purinergic P1 Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012120:Respiration Disorders / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D013806:Theophylline / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014158:Transcription, Genetic / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D011448:Prostaglandin Antagonists; D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline; D006655:Histone Deacetylases