Designing and Testing New Therapeutic Modalities for Treatment of Inflammatory Bowel Disease: Role of Experimental Animal Models
F. H. Mourad.
Experimental models of inflammatory bowel disease (IBD) have provided important information on the pathogenesis of this disease and tremendously helped in designing and testing some new treatment strategies. Every single step during the inflammatory process has been targeted to inhibit or induce a certain specific pathway. Among others, biologic therapy seems to be the most promising future therapy in IBD. Replenishing the microflora by probiotics showed beneficial results in experimental models. Agents that inhibit inflammatory cytokines and effector cells such as antibodies to tumor necrosis factor alpha, interleukin 12 (IL-12), interferon gamma and CD40L lymphocytes, as well as proinflammatory cytokines such as IL-10, IL-11 and transforming growth factor alpha were found to be effective in decreasing the inflammatory reaction in many animal models. Other candidates remain to be tested. A relatively new therapeutic approach is the blockade of effector cell recruitment into the lesions. In this regard, multiple agents were tested in animals and are already in clinical trials including antibodies to α4 integrins, to α4β7 integrins, to mucosal addressin cell adhesion molecule 1, and inhibitors of endothelial intercellular adhesion molecule 1 expression. Another approach aims at the use of growth factors such as growth hormone, trefoil factors and keratinocyte growth factors that have an important role in the healing of the inflamed intestine. Other strategies include transcription factor inhibitors, anti-coagulation and reactive oxygen scavengers. Herbal medicine has also been tried in animals and the possible mode of action has been investigated. Finally, new ways of delivering drugs, antibodies or anti-inflammatory cytokines to the site of inflammation using viral vectors, microsheres or lymphocytes are promising future approaches.
Keywords: inflammatory bowel disease, experimental colitis, cytokines, biologic therapy, probiotics, growth factors, adhesion molecules
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