Apoptosis of monocytes is not responsible for the therapeutic effects of infliximab. However, some of the therapeutic effects of infliximab may be caused by its ability to down-regulate proinflammatory cytokines production by monocytes exposed to bacterial antigens.
Crohn's disease and ulcerative colitis remain medically incurable conditions with potentially significant morbidity. The treatment of children with these conditions therefore should seek to reduce or eliminate symptoms, optimize nutritional status, promote normal growth and development, prevent complications, and minimize the potential psychologic effects of chronic illness. Treatment strategies must seek to both induce and maintain clinical remission. For all but the most mildly affected children with Crohn's disease, a combination of nutritional and pharmacologic approaches is optimal. For those with ulcerative colitis, anti-inflammatory medication is necessary. Moderate to severe Crohn's disease acutely responds best to potent immunomodulatory therapy, eg, corticosteroids and infliximab. Either agent must be coupled with 6-mercaptopurine or azathioprine to maintain long-term remission and to minimize toxicity. Particular attention must be paid to limit the growth suppression and other toxic effects of corticosteroids. Elemental or semielemental enteral nutrition also can induce remission effectively, but relapse is common after primary nutritional therapy is discontinued, mandating concomitant pharmacologic therapy with either 6-mercaptopurine or azathioprine. The availability of 6-mercaptopurine/azathioprine metabolite testing allows optimization of immunomodulatory therapy, detection of noncompliance, and avoidance of potentially dangerous toxicity. Mild ulcerative colitis acutely responds to treatment with a 5-aminosalicylate medication. Long-term remission frequently can be maintained with the same medication. Moderate to severe disease activity requires potent immunomodulatory therapy if colectomy is to be avoided. Surgery is a potential cure for patients with ulcerative colitis, although the development of pouchitis after ileal pouch anal anastomosis is common and frequently requires long-term medical management. Surgery provides only palliative relief of complications in those with Crohn's disease. Emerging therapies, especially evolving biologic and probiotic agents, offer hope for better treatments in the years ahead.
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