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
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.