title: Inhibitory activity of CX-659S, a novel diaminouracil derivative, against the rebound phenomenon following withdrawal of corticosteroid therapy for chronic contact hypersensitivity responses.
abstract: BACKGROUND
  CX-659S, a newly discovered anti-inflammatory compound, exerts inhibitory effects on chronic contact hypersensitivity responses (CHRs) induced by repeated application with picryl chloride (PC), which is known to mimic many, if not all, events occurring within lesional skin of patients with atopic dermatitis (AD). CX-659S suppresses the expression of mRNA for interleukin (IL)-4 and IL-10 but not that for IFN-gamma, and inhibits serum IgE production in a chronic CHR model. Although topical corticosteroids have been widely utilized in steroid-responsive dermatoses such as AD, their chronic use may be associated with significant side effects. In addition, a rebound phenomenon often occurs after discontinuation of prolonged use of topical corticosteroids, with enhanced production of IgE and Th2 cell cytokines. The purpose of this study was to assess whether CX- 659S inhibits the rebound phenomenon after discontinuation of chronic treatment with prednisolone in a chronic CHR model in mice.
  
  
  METHODS
  The efficacy of CX-659S as a sequential therapeutic agent after discontinuation of chronic treatment with prednisolone was tested on PC-treated ears of BALB/c mice with chronic CHR. Effects were quantified by measurements of ear thickness, serum IgE and cytokine mRNA expression.
  
  
  RESULTS
  The rebound phenomenon was confirmed after discontinuation of chronic treatment with prednisolone in chronic CHR in mice, i.e. by evidence of flare thickening of the ear, enhanced expression of mRNA for IL-4 and IL-10 and increased serum IgE. Sequentially applied CX-659S suppressed these rebound phenomena with a good cosmetic result.
  
  
  CONCLUSIONS
  CX-659S is the first promising compound with inhibitory activity on the rebound phenomenon following withdrawal of corticosteroid therapy without immunosuppression.
authors.affiliation: Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation, Toda, Saitama, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masakazu
authors.initials: M
authors.lastname: Isobe
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shiohara
authors.forename: Hideya
authors.initials: H
authors.lastname: Hayashi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology*; D003877:Dermatitis, Contact / Q000209:etiology; D005938:Glucocorticoids; D007052:Ibuprofen / Q000031:analogs & derivatives*; D007073:Immunoglobulin E / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009824:Ointments; D010853:Picryl Chloride; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D009824:Ointments; D007073:Immunoglobulin E; D014498:Uracil; D011239:Prednisolone; C052308:ibuprofen piconol; D007052:Ibuprofen; C418807:CX 659S; D010853:Picryl Chloride