CIRCULATING AND MUCOSAL CONCENTRATIONS OF TUMOR-NECROSIS-FACTOR AND INHIBITOR(S) IN CHRONIC INFLAMMATORY BOWEL-DISEASE

Monokines, in particular the interleukin-1 family and tumour necrosis factor alpha, have been implicated in the pathogenesis of chronic infl ammatory bowel disease. We initially assessed the circulating levels o f tumour necrosis factor alpha by ELISA in 20 patients with active Cro hn's disease, ten patients with active ulcerative colitis, and ten hea lthy volunteers. Circulating levels of tumour necrosis factor alpha di d not differ significantly between patients (median 80 pg/ml, range 0- 2.375) and healthy volunteers (median of 0 pg/ml, range 0-780) (p=0.16 ). If a limit of 40 pg/ml was applied, 21 of 30 patients had abnormal values compared to three out of ten controls (p=0.06), and for the sub group of patients with Crohn's disease, there was a significantly high er number of abnormal values as compared to controls (p<0.05), whereas no such difference was found for ulcerative colitis. A parallel study of ten Crohn's disease patients suggested that this result was not ex plained by differences in circulating tumour necrosis factor alpha inh ibitor levels (cytotoxicity assay). In a subsequent separate experimen t, mucosal levels of tumour necrosis factor alpha were measured in 31 patients with active chronic inflammatory bowel disease, 16 with Crohn 's disease and 15 with ulcerative colitis. Very low mucosal tumour nec rosis factor alpha values were detected in only three patients. Taken together, these results suggest that increased production of tumour ne crosis factor does not play a major role in the pathogenesis of chroni c inflammatory bowel disease.