Delayed addition of tumor necrosis factor (TNF) antagonists inhibits the generation of CD11c+ dendritic cells derived from CD34+ cells exposed to TNF-alpha.

Abstract

We have developed a method that cells exhibiting typical dendritic cell (DC) characteristics are generated from human CD34(+) cells and phagocytose cogenerating erythroid progenitor cells in the presence of tumor necrosis factor-alpha (TNF-alpha), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF antagonists, etanercept and infliximab, on TNF-alpha activity. We found that 1 microg/ml etanercept dramatically inhibited the generation of CD11c(+) cells accompanying with a complete recovery of the generation of erythroid progenitors. Infliximab at 200 microg/ml exhibited a similar effect to that observed for etanercept. The delayed addition of etanercept to this culture system at day five resulted in significant inhibitory effects on the generation of CD11c(+), CD4(+) and CD86(+) cells. These results indicate that TNF antagonists administered at a concentration that is achievable in vivo, neutralize the biologic effects of TNF-alpha in generating CD11c(+) cells and that a delay in the administration of these antagonists for as long as 5 days partially inhibits the biologic activity of TNF-alpha. These findings may contribute to a great understanding of anti-TNF therapy in patients with an overproduction of cytokines such as hemophagocytic syndromes.

DOI: 10.1007/s12185-009-0456-5

Cite this paper

@article{Guo2010DelayedAO, title={Delayed addition of tumor necrosis factor (TNF) antagonists inhibits the generation of CD11c+ dendritic cells derived from CD34+ cells exposed to TNF-alpha.}, author={Yong-Mei Guo and Makoto Hirokawa and Naoto Takahashi and Masumi Fujishima and Naohito Fujishima and Atsushi Komatsuda and Hiroyuki Tagawa and Hideaki Ohyagi and Yoshihiro Michishita and Kumi Ubukawa and Miwa Hebiguchi and Weiguo Xiao and Kenichi Sawada}, journal={International journal of hematology}, year={2010}, volume={91 1}, pages={61-8} }