title: Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis.
abstract: OBJECTIVE
  Mucosal cytokine profile determines T cell differentiation and may play an important role in the clinical course of inflammatory bowel disease (IBD). Cytokines from different T helper (Th) cell subsets are elevated in inflamed mucosa of patients with ulcerative colitis (UC), contributing to the inflammation. The aim of this study was to determine the predictive value of pre-treatment mucosal cytokine profile in response to therapy with the anti-TNF agent infliximab (IFX).
  
  
  METHODS
  The expression of Th1, Th17, Th2 and T-regulatory (Treg)-related cytokines was quantified by real-time PCR in mucosal biopsies from 74 UC patients before initiation of IFX induction therapy. Clinical and endoscopic effects were assessed after three infusions. Remission was defined as ulcerative colitis disease activity index (UCDAI) below 3.
  
  
  RESULTS
  Higher gene expression levels of IL-17A and IFN-γ were significantly associated with remission after three IFX infusions (OR = 5.4, p = 0.013 and OR = 5.5, p = 0.011, respectively). IL-17A and IFN-γ mRNA expression showed positive correlation. Th2 and Treg-related mediators were not significantly associated with clinical outcome, but were expressed at higher levels in UC patients compared with the controls. Immunohistochemistry (IHC) confirmed the presence of cells expressing both IL-17A and IFN-γ.
  
  
  CONCLUSIONS
  High expression of Th1- and Th17-related cytokines in the mucosa of UC patients can potentially predict a favorable outcome of IFX induction therapy. Th2 and Treg-related mediators do not appear useful as predictive markers.
authors.affiliation: Research Group of Gastroenterology and Nutrition, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. renathe.rismo@unn.no
authors.forename: Renathe
authors.initials: R
authors.lastname: Rismo
authors.forename: Trine
authors.initials: T
authors.lastname: Olsen
authors.forename: Guanglin
authors.initials: G
authors.lastname: Cui
authors.forename: Ingrid
authors.initials: I
authors.lastname: Christiansen
authors.forename: Jon
authors.initials: J
authors.lastname: Florholmen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Goll
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D020381:Interleukin-17; D012333:RNA, Messenger; D007371:Interferon-gamma; D000069285:Infliximab