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 TNFα, IL-8, TGFβ 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, 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).

Conclusion: 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.