NEUTRALIZATION OF TUMOR-NECROSIS-FACTOR (TNF) BUT NOT OF IL-1 REDUCESINFLAMMATION IN CHRONIC DEXTRAN SULFATE SODIUM-INDUCED COLITIS IN MICE

The cytokines TNF and IL-1 have been implicated as mediators of the in flammatory processes in patients with inflammatory bowel disease (IBD) . To investigate the role of these cytokines in mucosal inflammation w e used anti-cytokine strategies in a mouse model of acute and chronic colitis. Mice which received 5% dextran sulphate sodium (DSS) in their drinking water showed signs of acute colitis on day 4, with severe we ight loss and bloody diarrhoea. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days, with t he mice showing diarrhoea but no weight loss. In acute colitis, treatm ent with anti-IL-1 reagents, anti-TNF MoAb, or dexamethasone (DEX) led to aggravation. By contrast, in chronic colitis, treatment of mice wi th several IL-1 activity-inhibiting reagents failed to show significan t effects, whereas anti-TNF MoAb or DEX significantly reduced the coli tis. We conclude that in acute colitis IL-1 and TNF are beneficial, wh ereas in chronic colitis, TNF but not IL-1 seems to play a major role in perpetuation of chronic inflammation.