Tacrolimus hydrate ointment inhibits skin plasma extravasation in rats induced by topical m-xylene but not capsaicin

• Published in: European journal of pharmacology 2009-04, Vol.608 (1), p.91-96
• Main Authors: Goto, Shiho, Kondo, Fumio, Ikai, Yoshitomo, Miyake, Mio, Futamura, Masaki, Ito, Komei, Sakamoto, Tatsuo
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Capsaicin; Capsaicin - pharmacology; Dermis - cytology; Dose-Response Relationship, Drug; Immunosuppressive Agents - pharmacology; m-Xylene; Male; Mast cell degranulation; Mast Cells - drug effects; Mast Cells - pathology; Medical sciences; Neurogenic plasma extravasation; Ointments; Pharmacology. Drug treatments; Rats; Rats, Wistar; Skin - blood supply; Skin - drug effects; Specific Pathogen-Free Organisms; Tacrolimus - pharmacology; Tacrolimus ointment; Time Factors; Xylenes - blood; Xylenes - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.02.036

Tacrolimus ointment is used to treat various chronic inflammatory skin diseases. However, the effect of this ointment on acute neurogenic inflammation in the skin remains to be fully elucidated. Topical capsaicin and m-xylene produce tachykinin release from sensory nerves in the skin, resulting in skin plasma leakage. We investigated the effect of tacrolimus ointment (0.1%) on skin microvascular leakage induced by topical capsaicin (10 mM) and m-xylene (neat), and intracutaneous compound 48/80 (c48/80) (10 μg/ml, 50 μl/site) in two groups of rats pretreated with excessive capsaicin or its vehicle. The amount of leaked Evans blue dye reflected skin plasma leakage. Capsaicin, m-xylene or c48/80 was applied to the shaved abdomens of rats 8 h after topical application of tacrolimus ointment or its base. Desensitization with capsaicin reduced the skin response to capsaicin and m-xylene by 100% and 65%, respectively, but not to c48/80. Tacrolimus ointment significantly inhibited the skin response induced by m-xylene and c48/80, regardless of pretreatment with capsaicin. However, topical tacrolimus did not influence the skin response induced by capsaicin. We also evaluated whether topical capsaicin and m-xylene, and intracutaneous c48/80 cause mast cell degranulation in skin treated with tacrolimus. Mast cell degranulation was microscopically assessed. Topical tacrolimus only significantly suppressed degranulation induced by m-xylene and c48/80. Our data shows that tacrolimus ointment partially inhibits plasma leakage and mast cell degranulation in rat skin induced by m-xylene and c48/80 but not capsaicin, suggesting that the inhibitory effect is not associated with a reduction in neurogenic-mediated mechanisms.