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.
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.
Harada
Daisuke
D
Department of Allergy Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co. Ltd. 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Sizuoka 411-8731, Japan. daisuke.harada@kyowa.co.jp
Tsukumo
Yukihito
Y
Takashima
Yuko
Y
Manabe
Haruhiko
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002452:Cell Count; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010853:Picryl Chloride / Q000008:administration & dosage / Q000633:toxicity; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020889:Rolipram / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000473:pathology; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D010726:Phosphodiesterase Inhibitors; D007073:Immunoglobulin E; D016572:Cyclosporine; D011239:Prednisolone; D009195:Peroxidase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D010853:Picryl Chloride