Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity

Background: Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNF alpha, IL-8, TGF beta and other cytokines and characterised by neutrophil infiltration and tissue destruction. Aim: 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, TNF alpha, IL-17A, IL-8, IL-10, TGF beta and IFN gamma, 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 TGF beta 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 (r(s)=0.481, p<0.01) and TGF beta inversely correlated (r(s) = 0.462; p<0.01) with grade of inflammation. TNF alpha concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFN gamma (p<0.001), IL-4 (p<0.005) and IL-17A (p<0.002). Conclusion: Our findings suggest that IL-8 is elevated and TGF beta is reduced in distal colitis. Lower concentration of IFN gamma, IL-4 and IL-17A were also noted. TNF alpha levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGF beta mediated tissue healing. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.