IL-1 beta mediates diethyldithiocarbamate-induced granulocyte colony-stimulating factor production and hematopoiesis

Citation
Sm. Kennedy et Rf. Borch, IL-1 beta mediates diethyldithiocarbamate-induced granulocyte colony-stimulating factor production and hematopoiesis, EXP HEMATOL, 27(2), 1999, pp. 210-216
Citations number
46
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
EXPERIMENTAL HEMATOLOGY
ISSN journal
0301472X → ACNP
Volume
27
Issue
2
Year of publication
1999
Pages
210 - 216
Database
ISI
SICI code
0301-472X(199902)27:2<210:IBMDGC>2.0.ZU;2-0
Abstract
Diethyldithiocarbamate (DDTC) exhibits chemoprotective effects via reduced myelosuppression in mice treated with various chemotherapeutic agents. The mechanism of DDTC-mediated chemoprotection is believed to involve the induc tion and release of several cytokines, including interleukin-l beta (IL-1 b eta), tumor necrosis factor-alpha (TNF-alpha), and granulocyte colony-stimu lating factor (G-CSF), In the present study the roles of IL-1 beta and TNF- alpha in DDTC-mediated G-CSF induction were examined using human long-term bone marrow cultures (whLTBMCs), Administration of IL-1 receptor antagonist (IL-1ra) to DDTC-treated hLTBMCs obviated the G-CSF induction profile and blocked the resultant colony proliferation, indicating that IL-1 beta media tes DDTC-induced G-CSF release and hematopoiesis. IL-1 beta mRNA levels wer e increased threefold over control following DDTC treatment of hLTBMCs, imp lying that DDTC induces IL-1 beta at the level of transcription, Conversely , studies involving inhibition of DDTC-induced TNF-alpha synthesis, with th e inhibitor MNX 160, had no effect on DDTC-induced G-CSF release or colony proliferation. These findings taken together strongly suggest that IL-1 bet a mediates the chemoprotective effects of DDTC, (C) 1999 International Soci ety for Experimental Hematology. Published by Elsevier Science Inc.