The effect of etanercept and infliximab on the production of tumour necrosis factor alpha, interferon-gamma and GM-CSF in in vivo activated intestinal T lymphocyte cultures

Abstract

Background/aims: Infliximab (Ifx) is effective in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA), etanercept (Eta) in RA but not in CD. The mechanisms underlying these clinical differences are not fully understood, but this knowledge could be valuable to identify responders and develop new treatments. This study compares Eta and Ifx in vitro regarding transmembrane tumour necrosis factor alpha (tmb-TNF-alpha) expression and interferon-gamma (IFN-gamma), TNF-alpha and granulocyte macrophage colony stimulating factor (GM-CSF) production in intestinal T lymphocytes.

Methods: T lymphocyte cultures were established from biopsies from 10 CD patients and three healthy controls. The cytokine production and the expression of tmb-TNF-alpha were measured in the presence of Ifx/Eta.

Results: Eta and Ifx downregulated the production of IFN-gamma and GM-CSF in colonic T lymphocytes from CD patients and healthy controls. Both drugs bound tmb-TNF-alpha on activated T lymphocytes besides neutralising TNF-alpha, Eta less efficiently than Ifx (406 pg/ml (337-475); 133 pg/ml (119-147); p=0.004). TNF-alpha was detectable with the present assay in cell lines cultured in the presence of excess Eta.

Conclusions: We have established that Eta is just as efficient as Ifx in downregulating IFN-gamma and GM-CSF production in vitro and Eta bound to tmb-TNF-alpha. However, Eta bound the TNF-alpha molecule, important in CD, less efficiently than Ifx.