Secretion imbalance between tumour 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 disease (IBD).


OBJECTIVE
To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD.


METHODS
The secretion of TNF-alpha, TNF-beta, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD.


RESULTS
Spontaneous secretion of TNF-alpha in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-beta was higher in patients with Crohn's disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-alpha production correlated with severity of disease.


CONCLUSIONS
Results showed enhanced secretion of TNF-alpha but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.
Noguchi
M
M
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Hiwatashi
N
N
Liu
Z
Z
Toyota
T
T
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha