title: Upregulation of interleukin-12 and -17 in active inflammatory bowel disease.
abstract: BACKGROUND
  Cytokines are essential mediators of the intestinal inflammation during active episodes of inflammatory bowel disease (IBD). Interleukin (IL)-12 and IL-17 are potent immunoregulatory cytokines whose roles in the pathogenesis of IBD are unknown. The aim of this study was to evaluate the colonic expression of IL-12 and IL-17 genes in IBD.
  
  
  METHODS
  Fifty-one patients (22 with ulcerative colitis (UC), 17 with Crohn disease (CD), and 12 controls) who underwent colonoscopy were included. IBD disease activity was determined using a clinical grading scale. The degree of inflammation, as well as the content of CD4+ T cells (synthesizing IL-17) and CD68+ macrophages (synthesizing IL-12) in colonic biopsies, was determined. The amounts of IL-12 and IL-17 mRNA were assessed by RT-PCR, using GAPDH as an internal standard.
  
  
  RESULTS
  In colonic specimens, IL-17 mRNA expression was increased in moderately and severely active UC (P = 0.03) and in all degrees of activity in CD (P < 0.04). Levels of IL-12 mRNA were upregulated in both active UC and active CD compared to controls (P < 0.02). In cases of remission, IL-12 mRNA expression was similar to that found in control samples. Compared to controls, histological examination showed significant differences in signs of chronic and acute inflammation in UC (P < 0.01) and CD (P < 0.02), revealing a high correlation between clinical disease activity and histological scoring (r2 = 0.92, P < 0.005). Whereas CD4+ T cells were observed in lymphocyte aggregates located profound in the lamina propria, CD68+ macrophages were primarily found just underneath the surface epithelium. The density of CD4+ and CD68+ cells correlated significantly with the amounts of IL-17 and IL-12 mRNA, respectively (P < 0.05).
  
  
  CONCLUSIONS
  The expression of both IL-12 and IL-17 mRNA is induced in active UC and CD and may thus be involved in sustaining the intestinal inflammation in IBD. Inhibition of IL-12 or IL-17 might be future therapeutic targets in IBD.
authors.affiliation: Dept. of Gastroenterology C, Herlev Hospital, University of Copenhagen, Herlev, Denmark. ohn@dadlnet.dk
authors.forename: O H
authors.initials: OH
authors.lastname: Nielsen
authors.forename: I
authors.initials: I
authors.lastname: Kirman
authors.forename: N
authors.initials: N
authors.lastname: Rüdiger
authors.forename: J
authors.initials: J
authors.lastname: Hendel
authors.forename: B
authors.initials: B
authors.lastname: Vainer
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018664:Interleukin-12; D020381:Interleukin-17; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule