title: Antagonist effect of Interleukin 1 receptor on normal thymopoiesis and thymus toxicity of 5-azacytidine in mouse.
abstract: Thymopoiesis is essential and significant for development and maintenance of the robust and healthy immune system. The acute suppression of thymopoiesis induced by 5-Azacytidine (5-Aza) is an intractable clinical problem complicating chemotherapy. Interleukin 1 receptor antagonist (IL-1Ra) is a cytokine that competitively blocks binding of interleukin 1 (IL-1) to its receptor. This study aims to investigate the effects of the IL-1Ra on the thymus toxicity of 5-Aza in mouse. In this study, we treated the mice with the 5-Aza (100 mg/kg per mouse). The GeneChip methodology developed by Affymetrix was used to monitor global gene expression during mouse thymus regeneration induced by a single injection of 5-Aza. The total thymocytes were counted using a hemocytometer. Cell cycle of samples were analyzed on a Becton Dickinson FACScan. Cells surfaces were labeled with anti-CD4, anti-CD8 and anti-CD45RA antibodies, and detected by flow cytometry. BrdU incorporation was detected by flow cytometry. The results indicated that administering exogenous IL-1Ra to normal mice inhibited cell cycle progress of thymocytes in a dosage-dependent manner. Proliferation of immature CD4(-)CD8(-) double negative (DN) and CD4(+)CD8(+) double positive (DP) thymocytes were both inhibited. The pretreatment of normal mice with exogenous IL-1Ra reduced acute toxicity on thymus and immune suppression induced by 5-Aza. Furthermore, thymus reconstitution after 5-Aza treatment was accelerated by IL-1Ra. In conclusion, interleukin 1 receptor antagonist could inhibit normal thymopoiesis and reduce thymus toxicity of 5-azacytidine in mouse. Pretreatment with IL-1Ra would offer a new and promising strategy to alleviate immunotoxicity of chemotherapy in clinical.
authors.affiliation: Laboratory of Regeneration, School of Pharmacy, Shanghai Jiao Tong UniversityShanghai 200240, China; Shanghai Sine Pharmaceutical Laboratories Co, LtdShanghai 201206, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Yu
authors.affiliation: Laboratory of Regeneration, School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Wu
authors.affiliation: Shanghai Sine Pharmaceutical Laboratories Co, Ltd Shanghai 201206, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wen
authors.affiliation: Shanghai Sine Pharmaceutical Laboratories Co, Ltd Shanghai 201206, China.
authors.forename: Ningyun
authors.initials: N
authors.lastname: Sun
authors.affiliation: Laboratory of Regeneration, School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiang
authors.affiliation: Laboratory of Regeneration, School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Municipality Key Laboratory for Veterinary Biotechnology, School of Agriculture and Biotechnology, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Shunying
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Shanghai Municipality Key Laboratory for Veterinary Biotechnology, School of Agriculture and Biotechnology, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Shunyan
authors.initials: S
authors.lastname: Weng
authors.affiliation: Shanghai Municipality Key Laboratory for Veterinary Biotechnology, School of Agriculture and Biotechnology, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Laboratory of Regeneration, School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
keywords: 5-azacytidine; chemotherapy; interleukin 1 receptor antagonist; thymopoiesis