Anti-inflammatory effect of theophylline in rats and its involvement of the glucocorticoid-glucocorticoid receptor system.

Abstract

Although theophylline has been suggested to have an anti-inflammatory effect, there have been few reports to show the in vivo effect and the mechanism of anti-inflammatory activity of theophylline experimentally. To reveal the anti-inflammatory activity of theophylline, we studied the effect of theophylline and its metabolites on carrageenan-induced edema in rat foot pad. Subcutaneous injection of theophylline (5 - 100 mg/kg) inhibited carrageenan-induced edema dose-dependently. Theophylline metabolites, that is, 1-methylxanthine, 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid (equimolar dose to 50 mg/kg of theophylline), did not inhibit the edema significantly. The inhibitory effect of theophylline on carrageenan-induced edema disappeared by pretreatment with aminoglutethimide, an inhibitor of glucocorticoid synthesis and with mifepristone, an antagonist of the glucocorticoid receptor. These results suggest that theophylline itself has anti-inflammatory activity and the glucocorticoid-glucocorticoid receptor system is involved in the anti-inflammatory activity of theophylline.

• Authors: Shigekazu Watanabe, Jun Yamakami, Masao Tsuchiya, Tomoko Terajima, Junko Kizu, Seiji Hori
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 106 Issue 4 Pg. 566-70 (Apr 2008) ISSN: 1347-8613 [Print] Japan
• PMID: 18391482 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Glucocorticoids
• Hormone Antagonists
• Receptors, Glucocorticoid
• Aminoglutethimide
• Mifepristone
• Carrageenan
• Theophylline

Topics

• Aminoglutethimide (pharmacology)
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Carrageenan
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Edema (chemically induced, metabolism, prevention & control)
• Glucocorticoids (metabolism)
• Hormone Antagonists (pharmacology)
• Injections, Subcutaneous
• Male
• Mifepristone (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Glucocorticoid (drug effects, metabolism)
• Theophylline (administration & dosage, pharmacology)