Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infliximab, a chimeric antibody to tumour necrosis factor-alpha (TNF-alpha), 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-alpha) are of particular interest because of the crucial role of TNF-alpha 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-alpha neutralizing treatment include an increased susceptibility to apoptosis of intestinal mucosal T cells. A novel pathway of anti-TNF-alpha 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-alpha, resulted in a decreased production of GM-CSF (granulocyte-macrophage colony-stimulating factor) by T cells. Infliximab related down-regulation of TNF-alpha 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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PMID:Infliximab: mechanism of action beyond TNF-alpha neutralization in inflammatory bowel disease. 1520 77

The aim of this study was to analyze the change of serum cytokines and pentosidine levels in patients with rheumatoid arthritis (RA) by infliximab treatment. Twenty-three patients with RA were studied for 30 weeks on the effects of infliximab treatment. Serum levels of IL-15, IL-16, IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured with ELISA methods and pentosidine levels were determined using high-performance liquid chromatography, both at baseline and at 14 and 30 weeks after the initial treatment with infliximab. In addition, the patients also underwent physical and routine blood examinations. The higher levels of serum IL-15 in RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but serum IL-16, IL-17, GM-CSF, and pentosidine levels did not decrease. The serum IL-17 and GM-CSF levels remained to be a limited detectable level at the pre- and posttreatment with infliximab. Infliximab treatment significantly lowered the serum levels of IL-15 in patients with RA. IL-15 is one of the crucial cytokines affected by infliximab.
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PMID:Treatment with anti-TNF-alpha antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis. 1668 Mar 88