Infliximab: mechanism of action beyond TNF-α neutralization in inflammatory bowel disease

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Abstract

• Infliximab, a chimeric antibody to tumour necrosis factor-alpha (TNF-α), holds much promise for the treatment of patients with Crohn's disease.

• On the cellular level, infliximab affects survival and, as presented by Agnholt et al. in this issue of the journal, inhibits GM-CSF (granulocyte–macrophage colony-stimulating factor) production by intestinal T lymphocytes.

• Future studies will reveal whether the pro-apoptotic effect of infliximab is linked to its inhibition of endogenous GM-CSF expression in T cells.

Treatment of Crohn's disease, a severe chronic intestinal disorder, may at times be challenging as it can be refractory to routine therapy. Among novel therapeutic strategies, agents that neutralize tumour necrosis factor-alpha (TNF-α) are of particular interest because of the crucial role of TNF-α in sustaining chronic mucosal inflammation. The exact mechanism of the anti-TNF action, apart from direct activity that neutralizes cytokines, is not fully understood. Cellular effects of TNF-α neutralizing treatment include an increased susceptibility to apoptosis of intestinal mucosal T cells. A novel pathway of anti-TNF-α interaction with T cells has been presented in the current issue of this journal. Agnholt et al. have found that in-vivo or in-vitro administration of infliximab, a chimeric antibody to TNF-α, resulted in a decreased production of GM-CSF (granulocyte–macrophage colony-stimulating factor) by T cells. Infliximab related down-regulation of TNF-α induced GM-CSF expression may be one of the mechanisms by which this drug increases the rate of apoptosis in T cells.

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