Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 63, Issue 7, Pages 501-508Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2008.09.014
Keywords
5-Fluouracil; Interleukin 1 receptor antagonist; Myelosuppression
Funding
- National Natural Science Foundation of China [30572214]
- Science and Technology Commission of Shanghai Municipality [04DZI9203, 05DZI9319, 05PJ14074, 06dj14001]
- China Ministry of Science and Technology [863 2007AA02ZI49, 973 2007CB948004]
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5-Fluouracil (5-Fu) targeting of cycling hematopoietic cells results in bone marrow (BM) suppression. Interleukin I receptor antagonist (IL-1Ra) is a cytokine that competitively blocks the binding of interleukin I (IL-1) to its receptor. Unlike the supporting role of IL-1 less is known for the role of IL-1Ra in hematopoiesis. Here, we demonstrate that IL-1Ra expression in BM cells and in circulation was elevated temporarily during 5-Fu-induced myelosuppression. Exogenous IL-1Ra administered to normal mice reversibly inhibited cycling status of BM cells, and reduced the numbers of BM cells including colony-forming progenitor cells, white blood cells (WBCs), and platelets in a dosage-dependent and time-dependent fashion. Due perhaps to its reversible suppression of the cell cycle progression of BM cells, pretreatment of normal mice with exogenous IL-1Ra reduced the acute lethal toxicity and BM suppression of 5-Fu, and accelerated the recoveries of BM cells and platelets following 5-Fu treatment. Pretreatment with IL-1Ra offers a new promising strategy to alleviate the BM toxicity of chemotherapy in clinical settings. (C) 2008 Elsevier Masson SAS. All rights reserved.
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