Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity
Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFÎ±, IL-8, TGFÎ² and other cytokines and characterised by neutrophil infiltration and tissue destruction. To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls. 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, TNFÎ±, IL-17A, IL-8, IL-10, TGFÎ² and IFNÎ³ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation. 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 TGFÎ² 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 TGFÎ² inversely correlated (rs = 0.462; p < 0.01) with grade of inflammation. TNFÎ± concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNÎ³ (p < 0.001), IL-4 (p < 0.005) and IL-17A (p < 0.002). Our findings suggest that IL-8 is elevated and TGFÎ² is reduced in distal colitis. Lower concentration of IFNÎ³, IL-4 and IL-17A were also noted. TNFÎ± levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFÎ² mediated tissue healing.