The effect of 5-ASA and 4-ASA, drugs used for the treatment of
inflammatory bowel disease, on modulation of experimental
colitis and on colonic generation of
interleukin-1 was evaluated. Three weeks of treatment with 5-ASA or 4-ASA (50 micrograms/kg) and one week of treatment with 5-ASA significantly decreased colonic
interleukin-1 generation and the extent and severity of
inflammation in a rat model of
colitis induced by trinitrobenzene sulphonic
acid. Colonic biopsies were obtained from patients with active
ulcerative colitis and organ cultured 24 hours in the absence or presence of the following drugs:
sulphasalazine,
sulphapyridine, 5-ASA and 4-ASA (25-100 micrograms/ml).
Interleukin-1 content in tissue cultured in the presence of 5-ASA (100 micrograms/ml) was two-thirds of its content in tissue cultured in
drug free medium and its release into the medium was decreased by 50%.
Sulphasalazine 50 micrograms/ml significantly decreased by 33% the tissue content but did not affect
interleukin-1 release and a higher dose was not more effective.
Sulphapyridine and 4-ASA in doses up to 100 micrograms/ml did not affect either
interleukin-1 colonic content or its release into the culture medium. We conclude that pharmacological suppression of colonic
interleukin-1 generation may be one, although not the sole mechanism to explain the therapeutic efficacy of 5-ASA in the treatment of
inflammatory bowel disease.