title: Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity.
abstract: BACKGROUND
  Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.
  
  
  OBJECTIVE
  To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.
  
  
  METHODS
  Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age-sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann-Whitney U test and Spearman's correlation.
  
  
  RESULTS
  69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p<0.001; p<0.02) and control mucosa (p<0.001; p<0.001); IL-8 was positively correlated (rs=0.481, p<0.01) and TGFβ inversely correlated (rs=0.462; p<0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p<0.001), IL-4 (p<0.005) and IL-17A (p<0.002).
  
  
  CONCLUSIONS
  Our findings suggest that IL-8 is elevated and TGFβ is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing.
authors.affiliation: Department of Gastroenterology, Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Southwick Hill Road, Cosham, Portsmouth, PO63LY, UK. daniel.pearl@porthosp.nhs.uk
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pearl
authors.forename: Krina
authors.initials: K
authors.lastname: Shah
authors.forename: Mark A
authors.initials: MA
authors.lastname: Whittaker
authors.forename: Harriet
authors.initials: H
authors.lastname: Nitch-Smith
authors.forename: James F
authors.initials: JF
authors.lastname: Brown
authors.forename: Janis K
authors.initials: JK
authors.lastname: Shute
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Trebble
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D005938:Glucocorticoids