New therapies for inflammatory bowel disease: an update on chimeric anti-TNF alpha antibodies and IL-10 therapy.
In the past few years new concepts have been formulated for the therapeutic management of difficult-to-treat inflammatory bowel disease, based on better insights in the pathophysiological processes in inflamed colonic mucosa. TNF alpha, for example, has been shown to play a major role orchestrating several other cytokines and pathways in the immunological network. TNF alpha is a pro-inflammatory cytokine. In contrast, IL-10 is an anti-inflammatory cytokine. IL-10-deficient mice ('IL-10 knockout mice') will spontaneously develop enteritis in several parts of the digestive tract. Administration of IL-10 has been shown to improve and even to prevent the enteritis in these mice. One of the functions of IL-10 is to inhibit the TNF alpha production. Elimination of TNF alpha with anti-TNF alpha antibodies and administration of IL-10 is, therefore, thought to achieve healing of the inflamed mucosa in man as well. The first uncontrolled studies with intravenous administration of chimeric anti-TNF alpha antibodies and with human recombinant IL-10 are hopeful for the future management of patients with inflammatory bowel disease; particularly since a fast healing of colonic mucosa was demonstrated and no serious adverse events were described. One has to be aware, however, of allergic reactions to the 'foreign' peptide. Because of rapid fibrosing and scarring in a narrow lumen, e.g. the ileum, stenosis formation could take place. In one described case a surgical intervention was needed because of this complication. For the near future these new and potent drugs seem very promising, although at present they are only available for trials with Crohn's disease patients. Certainly, in the coming years more immunomodulating drugs will be developed for use in man.
van Hogezand
R A
RA
Dept. of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands.
Verspaget
H W
HW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000628:therapy*; D016753:Interleukin-10 / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10