Interleukin 1 receptor antagonist inhibits normal hematopoiesis and reduces lethality and bone marrow toxicity of 5-fluouracil in mouse

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.