title: Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis.
abstract: BACKGROUND
  It has been suggested that Crohn's disease (CD) is associated with an exaggerated T-helper 1 cytokine response manifested by increased production of interleukin (IL)-12. IL-12 is a heterodimeric protein comprising 2 disulfide-linked subunits designated p35 and p40. Recently, IL-12-related cytokines, IL-23 and IL-27, were described. Biologically active IL-23 is a heterodimer whose p40 subunit is identical to IL-12p40 whereas its p19 subunit is distantly related to IL-12p35. IL-27 consists of EBI3, an IL-12p40-related protein, and p28, a newly discovered IL-12p35-related polypeptide.
  
  
  OBJECTIVE
  We sought to determine whether mucosal expression of IL-23p19 and IL-27p28 transcripts correlate with the inflammatory activity in inflammatory bowel disease (IBD).
  
  
  METHODS
  Messenger RNA expression in colonic mucosa from patients with Crohn's disease (CD; n = 37) and ulcerative colitis (UC; n = 19), and in non-IBD control subjects (specific colitis [SC]; n = 16) and normal, nondiseased control patients (n = 12) was measured by reverse-transcribed real-time polymerase chain reaction.
  
  
  RESULTS
  IL-23p19 was significantly increased in inflamed mucosa in CD (P = 0.0377) and to a lesser extent also in UC patients but not in SC patients. Elevation of IL-23p19 transcript levels in CD correlated with the severity of endoscopic lesions. IL-27p28 transcripts and EBI3 transcripts were significantly elevated only in active CD.
  
  
  CONCLUSIONS
  IL-23p19, IL-27p28, and EBI3 transcripts are strongly up-regulated in CD. The stimulatory effects of these cytokines on naive T cells in addition to a strongly synergistic action with IL-12 to trigger interferon-gamma production may contribute to the perpetuation of the inflammatory process in patients with CD. Notably, increased expression of IL-23 and IL-27 transcripts in CD suggests a T helper 1-dominated immunologic function in this disease.
authors.affiliation: Department of Internal Medicine II , Saarland University, Homburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Bianca
authors.initials: B
authors.lastname: Ludwig
authors.forename: Ina
authors.initials: I
authors.lastname: Mueller-Molaian
authors.forename: Thomas
authors.initials: T
authors.lastname: Marth
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Meuer
authors.forename: Andreas
authors.initials: A
authors.lastname: Stallmach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism*; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; C464565:MYDGF protein, human; D012333:RNA, Messenger