1. Effect of orally administered rolipram, a phosphodiesterase 4 inhibitor, on a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application
- Author
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Yukihito Tsukumo, Yuko Takashima, Haruhiko Manabe, and Daisuke Harada
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Phosphodiesterase Inhibitors ,Prednisolone ,T-Lymphocytes ,Lymphocyte ,Anti-Inflammatory Agents ,Administration, Oral ,Cell Count ,Dermatitis ,Picryl Chloride ,Weight Gain ,Immunoglobulin E ,Mice ,Oral administration ,Internal medicine ,medicine ,Animals ,Rolipram ,Peroxidase ,Pharmacology ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,biology ,Chemistry ,Interleukin ,Phosphodiesterase ,Cyclic Nucleotide Phosphodiesterases, Type 4 ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,3',5'-Cyclic-AMP Phosphodiesterases ,Enzyme inhibitor ,Ear, Inner ,Cyclosporine ,biology.protein ,Cytokines ,Lymph Nodes ,Immunosuppressive Agents ,medicine.drug - Abstract
The purpose of this study was to evaluate the efficacy of rolipram, a phosphodiesterase (PDE) 4 inhibitor, in a mouse model of dermatitis induced by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). BALB/c mice were sensitized with 0.3% w/v TNCB applied to the ear on day -7, followed by application three times a week from day 0. Rolipram, prednisolone and cyclosporine A were administered orally once daily from day 0 to 21. Rolipram at a dose of 10 mg/kg/day significantly inhibited the ear thickness and the increase in cytokine levels and enzyme activity in the ear. Interleukin (IL)-4 production was markedly decreased in cervical lymph node cells from animals treated with rolipram at a dose of 10 mg/kg/day. Prednisolone and cyclosporine A significantly reduced ear thickness. These compounds significantly decreased the total cell and lymphocyte number of the cervical lymph nodes. Furthermore, prednisolone markedly suppressed body weight gain, and cyclosporine A significantly increased the serum total IgE concentration compared with that in the vehicle-treated control. Rolipram, unlike prednisolone and cyclosporine A, did not influence body weight and the total IgE concentration in the serum. The present results suggest that the PDE4 inhibitor is a promising oral medicine for the treatment of chronic skin inflammatory diseases.
- Published
- 2006