Anti-inflammatory effect of theophylline in rats and its involvement of the glucocorticoid-glucocorticoid receptor system.
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.
Watanabe
Shigekazu
S
Department of Practical Pharmacy, Kyoritsu University of Pharmacy, Minato-ku, Tokyo, Japan.
Yamakami
Jun
J
Tsuchiya
Masao
M
Terajima
Tomoko
T
Kizu
Junko
J
Hori
Seiji
S
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005938:Glucocorticoids / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism*; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D000616:Aminoglutethimide; D015735:Mifepristone; D002351:Carrageenan; D013806:Theophylline