Increased production of matrix metalloproteinase-3 and tissue inhibitor ofmetalloproteinase-1 by inflamed mucosa in inflammatory bowel disease

Inflammatory bowel diseases (IBD) are characterized by a sustained inflamma tory cascade that gives rise to the release of mediators capable of degradi ng and modifying bowel wall structure. Our aims were (i) to measure the pro duction of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, ti ssue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty -eight patients with IBD, including 25 with Crohn's disease and 13 with ulc erative colitis, were included. Ten controls were also studied. Biopsies we re taken from inflamed and uninflamed regions and inflammation was graded b oth macroscopically and histologically. Organ cultures were performed for 1 8 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1 beta, IL-10, MMP- 3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below t he sensitivity of our immunoassay in the vast majority of uninflamed sample s either from controls or from those with Crohn's disease or ulcerative col itis. In inflamed mucosa, the production of these mediators increased signi ficantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulc erative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflamma tory cytokines and IL-10, as well as with the degree of macroscopic and mic roscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerati ve colitis show increased production of both MMP-3 and its tissue inhibitor , which correlates very well with production of IL-1 beta, IL-6, TNF-alpha and IL-10.