title: Expression of IL-2, IL-17 and TNF-alpha in patients with Crohn's disease treated with anti-TNF antibodies.
abstract: BACKGROUND
  The T cell cytokine IL-17 and the Th-17 pathway appear to have a role in the pathogenesis of inflammatory bowel diseases. IL-2 is a potent stimulator of lymphocyte proliferation and IL2/IL21 receptor polymorphisms have recently been associated with susceptibility to IBD.
  
  
  OBJECTIVE
  To evaluate the expression of IL-17, IL-2 and TNFα in Crohn's disease (CD) patients with and without anti-TNFs.
  
  
  METHODS
  Cytokine expression was evaluated by ELISA and intracellular staining of CD4(+) T-cells from the peripheral blood and lamina propria of CD patients and of non-IBD controls. The results were stratified by disease activity and anti-TNF treatment.
  
  
  RESULTS
  IL2 expression was significantly elevated in CD patients not treated with anti-TNFs in comparison to healthy controls (19.6% vs. 33.3%, P=0.03) and CD patients treated with anti-TNFs (20.4% vs. 33.3%, P=0.02), and similar in infliximab-treated patients and controls. IL17 expression was similar in CD patients and controls, and was not affected by anti-TNF therapy. TNFα expression in patients with active CD was increased compared to controls (35.5% vs 25.7%, P<0.005), and was significantly decreased in anti-TNF treated patients in comparison to CD patients without anti-TNFs (39.6% vs 26.2%, P=0.01).
  
  
  CONCLUSIONS
  Expression of IL2 was significantly decreased in anti-TNF-treated CD patients in comparison to non-treated CD patients and controls. This novel finding may indicate a further mechanism of anti-TNF therapy in CD. Expression of IL17 was not influenced by presence of CD or anti-TNF therapy, which may partly explain the failure of recent clinical trials investigating anti-IL17 therapy in CD.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Lior H
authors.initials: LH
authors.lastname: Katz
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel. Electronic address: ukopylov@gmail.com.
authors.forename: Uri
authors.initials: U
authors.lastname: Kopylov
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Fudim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Yavzori
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Picard
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Department of Gastroenterology, Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D000069285:Infliximab; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab