Clinical-alimentary tractInfliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease☆
Section snippets
Cell culture
All cells were cultured at 37°C, 5% CO2, and 99% humidity. Three culture media were used. Complete Iscove’s modified Dulbecco’s medium (Life Technologies, Paisley, Scotland) contained gentamicin (86 μg/mL; Duchefa, Haarlem, The Netherlands), 1% heat inactivated fetal calf serum (HyClone, Logan, UT), and l-glutamine (29.2 mg/mL; Gibco, Rhode Island, NY) for monocyte-derived dendritic cells. Complete Dulbecco’s modified Eagle medium (BioWhittaker, Verviers, Belgium) was supplemented with 5% fetal
Infliximab and etanercept neutralize recombinant human TNF-α effectively
A reason for the difference between infliximab and etanercept in Crohn’s disease could be related to a difference in TNF-α-neutralizing potential between the 2 drugs. Hence, we assayed the TNF-α-neutralizing potential of infliximab and etanercept both with respect to TNF-α-dependent transactivation of a NF-κB-driven reporter construct as well as in the WEHI assay for TNF-α-induced cell death. Infliximab abolished TNF-α-induced GFP expression in NF-κB reporter construct transfected HeLa cells at
Discussion
The cytokine TNF-α is believed to play a key role in the pathogenesis of acute and chronic inflammatory diseases. TNF-α-neutralizing antibodies have proved to be effective in various animal models; 2 therapeutic agents, infliximab (a chimeric monoclonal anti-TNF-α antibody) and etanercept (a recombinant human TNF receptor fusion protein), have been approved for clinical use. Both TNF-α-neutralizing agents have shown high efficacy in rheumatoid arthritis,17, 33 but only infliximab is efficacious
Acknowledgements
The authors thank Dr. David Shealy for providing the C17-1a antibody as well as for helpful discussions and critical reading of the manuscript, Prof. Marc Feldmann for the WEHI cells, Frederik Slors for providing intestinal specimen, and Eric van Tol, Hilde Croes, Inge Pronk and Ludo Evers for their assistance with the experiments.
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Supported by an unrestricted educational grant from Johnson & Johnson (to J.M.H.V.), an unrestricted educational grant from Numico Research b.v. (to H.B.), the Amsterdam Medical Center Research b.v. (to G.R.V. and H.H.V.), the Meelmeijer Foundation (to C.V.), the Dutch Heart Foundation (99.188 to I.H.), and the Dutch Cancer Foundation (99.30 to M.P.P.).