SECRETION IMBALANCE BETWEEN TUMOR-NECROSIS-FACTOR AND ITS INHIBITOR IN INFLAMMATORY BOWEL-DISEASE

Background-Tumour necrosis factor (TNF) alpha and TNF-beta are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel d isease (IBD). Aims-To test the hypothesis that an imbalance in secreti on between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD. Methods-The secretion of TNF-alpha, TNF-beta, and s oluble TNF receptors was compared in the culture supernatants of colon ic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD. Results-Spontaneous secretion of TN F-alpha in involved IBD mucosa was higher than in normal control and s elf limited colitis mucosa. Secretion of TNF-beta was higher in patien ts with Crohn's disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble rec eptor release from IBD mucosa was increased in active inflammation; re lease from lamina propria cells was not increased. Mucosal TNF-alpha p roduction correlated with severity of disease. Conclusions-Results sho wed enhanced secretion of TNF-alpha but failure to release enhanced am ounts of soluble TNF receptor in lamina propria mononuclear cells of p atients with IBD. An imbalance in secretion between TNF and TNF inhibi tor may be implicated in the pathogenesis of IBD.