title: Down-regulation of IL-12 by topical corticosteroids in chronic atopic dermatitis.
abstract: BACKGROUND
  Previous reports indicate that IL-12 may be involved in the development of chronic atopic dermatitis. However, the cellular source of this cytokine in the skin and its expression during successful treatment of the skin lesions are not known.
  
  
  OBJECTIVE
  Our purpose was to delineate the precise in situ localization of IL-12 and its modulation under topical treatment with corticosteroids.
  
  
  METHODS
  Skin biopsy specimens were obtained from nonlesional, lesional, and treated skin of patients with atopic dermatitis and from healthy skin of nonatopic control subjects. IL-12 was investigated by real-time quantitative reverse transcriptase-PCR and immunohistochemistry.
  
  
  RESULTS
  Expression of IL-12 p40 mRNA was significantly enhanced in lesional skin from atopic dermatitis and strongly down-regulated after treatment with topical corticosteroids for 9 to 10 days. In contrast, similar levels of IL-12 p35 transcripts were found in all the samples without any significant differences after treatment. In addition, a strong enhancement of IL-12 immunoreactivity was observed on the mononuclear cell infiltrate in the lesional skin samples, which was also markedly reduced after treatment. IL-12 immunoreactivity was mainly located in the cytoplasm of dermal dendritic cells and macrophages as well as some Langerhans cells.
  
  
  CONCLUSIONS
  Our data suggest that the enhanced local production of IL-12 in dendritic cells and macrophages may be responsible for up-regulating production of IFN-gamma in chronic lesions and strengthen the idea that IL-12 may have a pivotal role in promoting inflammation in atopic dermatitis.
authors.affiliation: Dermatological Clinic and the Clinic for Rheumatology and Clinical Immunology/Allergology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Yawalkar
authors.forename: S
authors.initials: S
authors.lastname: Karlen
authors.forename: F
authors.initials: F
authors.lastname: Egli
authors.forename: C U
authors.initials: CU
authors.lastname: Brand
authors.forename: H U
authors.initials: HU
authors.lastname: Graber
authors.forename: W J
authors.initials: WJ
authors.lastname: Pichler
authors.forename: L R
authors.initials: LR
authors.lastname: Braathen
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002461:Cell Line, Transformed; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007124:Immunoenzyme Techniques; D018664:Interleukin-12 / Q000235:genetics*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger; D011817:Rabbits; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D018664:Interleukin-12