title: Narrowband (312-nm) UV-B suppresses interferon gamma and interleukin (IL) 12 and increases IL-4 transcripts: differential regulation of cytokines at the single-cell level.
abstract: OBJECTIVE
  To determine whether 312-nm UV-B alters production of effector and regulatory cytokines by viable T cells that remain in psoriatic lesions during UV-B phototherapy.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  General clinical research center of The Rockefeller University Hospital.
  
  
  METHODS
  Ten adult patients with moderate to severe psoriasis vulgaris that was difficult to manage were sequentially enrolled in our protocols, and biopsies were taken at various time points from resolving lesions.
  
  
  METHODS
  Narrowband (312-nm) UV-B was given starting at 50% of a minimum erythema dose, then increased daily 10% to 15% if no apparent erythema was induced. Patients continued with treatment until maximal benefit was noted. In some experiments, T cells were irradiated ex vivo with standard TL-01 fluorescent bulbs (Philips Lighting Co, Somerset, NJ).
  
  
  METHODS
  Intracellular cytokine staining was done using flow cytometry to quantify numbers of cytokine-producing cells from epidermal and peripheral T cells. The production of messenger RNA for interleukin (IL) 12, interferon (IFN) gamma, tumor necrosis factor alpha, IL-4, and IL-10 was measured by quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Ultraviolet-B treatment eliminated production of IL-12 messenger RNA and decreased production of IFN-gamma messenger RNA by more than 60% in irradiated psoriasis lesions (P<.03 for both). Within 1 to 2 weeks of starting UV-B treatment, the frequency of viable T cells producing IFN-gamma decreased 40% to 65%. In contrast, mRNA for IL-4 increased by 82% (P =.05) during UV-B treatment, and the number of IL-4-producing cells increased by 228% after 1 week of treatment. In vitro experiments established that, on the single-cell level, survival and cytokine production by type 1 T cells were differentially regulated by UV-B.
  
  
  CONCLUSIONS
  Therapeutic UV-B suppresses the type 1 (proinflammatory) axis as defined by IL-12, IFN-gamma, and IL-8, and can selectively reduce proinflammatory cytokine production by individual T cells. Knowledge of the immunomodulatory effects of UV-B will help to integrate this modality in future therapeutics for psoriasis based on deliberate blockade of inflammatory molecular pathways in the type 1 T-cell pathway.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10021-6399, USA.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Walters
authors.forename: Maki
authors.initials: M
authors.lastname: Ozawa
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: William L
authors.initials: WL
authors.lastname: Trepicchio
authors.forename: Judith
authors.initials: J
authors.lastname: Bliss
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001707:Biopsy, Needle; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000528:radiation effects*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000528:radiation effects*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000528:radiation effects*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D011446:Prospective Studies; D011565:Psoriasis / Q000473:pathology* / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000502:physiology / Q000528:radiation effects; D014467:Ultraviolet Therapy / Q000379:methods*
chemical_list: D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma