Delayed addition of tumor necrosis factor (TNF) antagonists inhibits the generation of CD11c+ dendritic cells derived from CD34+ cells exposed to TNF-alpha.
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.
Guo
Yong-Mei
YM
Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Hirokawa
Makoto
M
Takahashi
Naoto
N
Fujishima
Masumi
M
Fujishima
Naohito
N
Komatsuda
Atsushi
A
Tagawa
Hiroyuki
H
Ohyagi
Hideaki
H
Michishita
Yoshihiro
Y
Ubukawa
Kumi
K
Hebiguchi
Miwa
M
Xiao
Weiguo
W
Sawada
Kenichi
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D000068800:Etanercept; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D000069285:Infliximab; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D051359:Lymphohistiocytosis, Hemophagocytic / Q000188:drug therapy* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D051940:B7-2 Antigen; D039521:CD11c Antigen; D015704:CD4 Antigens; C497964:CD86 protein, human; C115022:IL3RA protein, human; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053650:Interleukin-3 Receptor alpha Subunit; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept