Thrombopoietin protects mice from mortality and myelosuppression following high-dose irradiation: importance of time scheduling

• Published in: Canadian journal of physiology and pharmacology Vol. 80; no. 7; pp. 717 - 721
• Main Authors: Mouthon, Marc-André, Van der Meeren, Anne, Vandamme, Marie, Squiban, Claire, Gaugler, Marie-Hélène
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Ottawa, Canada NRC Research Press 01.07.2002; National Research Council of Canada; Canadian Science Publishing NRC Research Press
• Subjects: Animals; Biological and medical sciences; Blood Cell Count; Blood. Blood coagulation. Reticuloendothelial system; Dose-Response Relationship, Drug; Granulocytes - drug effects; Hematopoiesis - drug effects; Hematopoietic Stem Cells - physiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Physiological aspects; Radiation; Radiation Injuries, Experimental - blood; Radiation Injuries, Experimental - drug therapy; Survival Analysis; Thrombopoietin - therapeutic use; Time Factors; Treatment efficiency; Rodentia; Survival; Thrombopoietin; Lethal dose; Vertebrata; Mammalia; Mouse; Hematopoiesis; Animal; Irradiation; Myelosuppression; Timing
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y02-090

Thrombopoietin is the major regulator of platelet production and a stimulator of multilineage hematopoietic recovery following irradiation. The efficacy of three different schedules of thrombopoietin administration was tested on blood cell counts, hematopoietic bone marrow progenitors, and 30-day animal survival in C57BL6/J mice receiving a total body irradiation, with doses ranging from 7 to 10 Gy. A single dose of murine thrombopoietin was injected 2 h before, 2 h after, or 24 h after irradiation. Thrombopoietin promoted multilineage hematopoietic recovery in comparison to placebo up to 9 Gy at the level of both blood cells and bone marrow progenitors, whatever the schedule of administration. The injection of thrombopoietin 2 h before or 2 h after irradiation equally led to the best results concerning hematopoietic recovery. On the other hand, thrombopoietin administration promoted 30-day survival up to 9 Gy with the highest efficacy obtained when thrombopoietin was injected either 2 h before or 2 h after irradiation. However, when its injection was delayed at 24 h, thrombopoietin had almost no effect on survival of 9 Gy irradiated mice. Altogether, our results show that the time schedule for thrombopoietin injection is of critical importance and when thrombopoietin is administered before or shortly after irradiation, it efficiently promotes mice survival to supra-lethal irradiation (up to 9 Gy) in relation with hematopoietic recovery.Key words: irradiation, thrombopoietin, survival, hematopoiesis.