Neutralization of tumour necrosis factor (TNF) but not of IL‐1 reduces inflammation in chronic dextran sulphate sodium‐induced colitis in mice

The cytokines TNF and IL‐1 have been implicated as mediators of the inflammatory processes in patients with inflammatory bowel disease (IBD). To investigate the role of these cytokines in mucosal inflammation we 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 weight loss and bloody diarrhoea. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days, with the mice showing diarrhoea but no weight loss. In acute colitis, treatment with anti‐IL‐1 reagents, anti‐TNF MoAb, or dexamethasone (DEX) led to aggravation. By contrast, in chronic colitis, treatment of mice with several IL‐1 activity‐inhibiting reagents failed to show significant effects, whereas anti‐TNF MoAb or DEX significantly reduced the colitis. We conclude that in acute colitis IL‐1 and TNF are beneficial, whereas in chronic colitis, TNF but not IL‐1 seems to play a major role in perpetuation of chronic inflammation.

[1]  A. Feller,et al.  Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene , 1993, Cell.

[2]  R. Coffman,et al.  Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. , 1994, Immunity.

[3]  A. Mantovani,et al.  The type II 'decoy' receptor: a novel regulatory pathway for interleukin 1. , 1994, Immunology today.

[4]  C. Fiocchi,et al.  Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. , 1995, Journal of immunology.

[5]  D. Remick,et al.  Anti-tumor necrosis factor antibody therapy fails to prevent lethality after cecal ligation and puncture or endotoxemia. , 1992, Journal of immunology.

[6]  D. Remick,et al.  Antiserum to Tumor Necrosis Factor and Failure to Prevent Murine Colitis , 1995, Journal of pediatric gastroenterology and nutrition.

[7]  A. Munakata,et al.  The role of proinflammatory and immunoregulatory cytokines in the pathogenesis of ulcerative colitis. , 1995, Journal of gastroenterology.

[8]  S. Targan,et al.  Triggered human mucosal T cells release tumour necrosis factor‐alpha and interferon‐gamma which kill human colonic epithelial cells , 1991, Clinical and experimental immunology.

[9]  K. Rajewsky,et al.  Interleukin-10-deficient mice develop chronic enterocolitis , 1993, Cell.

[10]  P. Simon,et al.  Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease. , 1990, Gut.

[11]  S. Waugh,et al.  Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. , 1991, Journal of immunology.

[12]  A. Cooke,et al.  Tumour necrosis factor‐alpha and interferon‐gamma production measured at the single cell level in normal and inflamed human intestine , 1990, Clinical and experimental immunology.

[13]  A. Baldwin,et al.  Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids , 1995, Science.

[14]  M. Neurath,et al.  Antibodies to interleukin 12 abrogate established experimental colitis in mice , 1995, The Journal of experimental medicine.

[15]  A. Baldwin,et al.  Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. , 1995, Science.

[16]  Y. Mahida,et al.  Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. , 1989, Gut.

[17]  K. Mitsuyama,et al.  IL‐8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease , 1994, Clinical and experimental immunology.

[18]  S. Schreiber,et al.  Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. , 1993, Clinical and experimental immunology.

[19]  H. Towbin,et al.  Neutralization of interleukin-1 beta activity in vivo with a monoclonal antibody alleviates collagen-induced arthritis in DBA/1 mice and prevents the associated acute-phase response. , 1993, Clinical and experimental rheumatology.

[20]  C. Nast,et al.  Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis. , 1990, The Journal of clinical investigation.

[21]  C. Beglinger,et al.  Platelets in ulcerative colitis and Crohn's disease express functional interleukin‐1 and interleukin‐8 receptors , 1994, European journal of clinical investigation.

[22]  D. Hommes,et al.  Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). , 1995, Gastroenterology.

[23]  A. Levine,et al.  Interleukin 4 in inflammatory bowel disease and mucosal immune reactivity. , 1996, Gastroenterology.

[24]  B. Echtenacher,et al.  Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. , 1990, Journal of immunology.

[25]  B. Echtenacher,et al.  Critical protective role of mast cells in a model of acute septic peritonitis , 1996, Nature.

[26]  M. Feldmann,et al.  Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.