Delayed addition of tumor necrosis factor (TNF) antagonists inhibits the generation of CD11c+ dendritic cells derived from CD34+ cells exposed ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-12-12

AUTHORS

Yong-Mei Guo, Makoto Hirokawa, Naoto Takahashi, Masumi Fujishima, Naohito Fujishima, Atsushi Komatsuda, Hiroyuki Tagawa, Hideaki Ohyagi, Yoshihiro Michishita, Kumi Ubukawa, Miwa Hebiguchi, Weiguo Xiao, Kenichi Sawada

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-α (TNF-α), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF antagonists, etanercept and infliximab, on TNF-α activity. We found that 1 μg/ml etanercept dramatically inhibited the generation of CD11c+ cells accompanying with a complete recovery of the generation of erythroid progenitors. Infliximab at 200 μg/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-α 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-α. These findings may contribute to a great understanding of anti-TNF therapy in patients with an overproduction of cytokines such as hemophagocytic syndromes. More... »

PAGES

61-68

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-009-0456-5

DOI

http://dx.doi.org/10.1007/s12185-009-0456-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041590354

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20012512


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27 schema:description 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-α (TNF-α), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF antagonists, etanercept and infliximab, on TNF-α activity. We found that 1 μg/ml etanercept dramatically inhibited the generation of CD11c+ cells accompanying with a complete recovery of the generation of erythroid progenitors. Infliximab at 200 μg/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-α 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-α. These findings may contribute to a great understanding of anti-TNF therapy in patients with an overproduction of cytokines such as hemophagocytic syndromes.
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34 CD4
35 CD86
36 TNF antagonists
37 TNF-α activity
38 activity
39 addition
40 addition of etanercept
41 administration
42 antagonist
43 anti-TNF therapy
44 biologic activity
45 biologic effects
46 cell characteristics
47 cell factor
48 cells
49 characteristics
50 complete recovery
51 concentration
52 culture system
53 cytokines
54 day five
55 days
56 delay
57 dendritic cell characteristics
58 dendritic cells
59 effect
60 erythroid progenitor cells
61 erythroid progenitors
62 erythropoietin
63 etanercept
64 factors
65 findings
66 five
67 generation
68 greater understanding
69 hemophagocytic syndrome
70 human CD34
71 infliximab
72 inhibitory effect
73 interleukin-3
74 method
75 necrosis factor
76 overproduction
77 overproduction of cytokines
78 patients
79 phagocytose
80 presence
81 progenitor cells
82 progenitors
83 recovery
84 results
85 significant inhibitory effect
86 similar effects
87 stem cell factor
88 syndrome
89 system
90 therapy
91 tumor necrosis factor
92 understanding
93 vivo
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