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

TY - JOUR

T1 - Infliximab

T2 - Mechanism of action beyond TNF-α neutralization in inflammatory bowel disease

AU - Kirman, Irena

AU - Whelan, Richard L.

AU - Nielsen, Ole H.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - 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.

AB - 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.

KW - Crohn's disease

KW - Granulocyte-macrophage colony-stimulating factor

KW - Infliximab

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=3142559655&partnerID=8YFLogxK

U2 - 10.1097/01.meg.0000108345.41221.c2

DO - 10.1097/01.meg.0000108345.41221.c2

M3 - Journal article

C2 - 15201575

AN - SCOPUS:3142559655

SN - 0954-691X

VL - 16

SP - 639

EP - 641

JO - European Journal of Gastroenterology and Hepatology, Supplement

JF - European Journal of Gastroenterology and Hepatology, Supplement

IS - 7

ER -