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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-06-1634. This Article Full Text (PDF) All Versions of this Article: 2002-06-1634v1 101/7/2609    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Herodin, F. J Articles by Drouet, M. Search for Related Content PubMed PubMed Citation Articles by Herodin, F. J Articles by Drouet, M. Social Bookmarking                   What's this? Submitted June 3, 2002 Accepted November 22, 2002 SHORT-TERM INJECTION OF ANTIAPOPTOTIC CYTOKINE COMBINATIONS SOON AFTER LETHAL GAMMA IRRADIATION PROMOTES SURVIVAL Francis J Herodin*, Philippe Bourin, Jean-Francois Mayol, Jean-Jacques Lataillade, and Michel Drouet Radiobiology, CRSSA, La Tronche, France Immunology, CTSA, Clamart, France * Corresponding author; email: francis.herodin{at}wanadoo.fr. Recovery from radiation-induced (RI) myelosuppression depends on hematopoietic stem and progenitor cell survival and the active proliferation/differentiation process, which requires early cytokine support. Single cytokine or late-acting growth factor therapy have proved to be rather inefficient in ensuring reconstitution after severe RI damage. This work was aimed at evaluating the in vivo survival effect of combinations of early-acting cytokines whose antiapoptotic activity has been demonstrated in vitro: SCF (S), FLT-3 ligand (F), TPO (T), IL-3 (3) and SDF-1. B6D2F1 mice were total body irradiated at 8 Gy of 137Cs radiation (i.e. lethal dose 90% at 30 days) and treated soon after irradiation, at 2 hours and 24 hours, with recombinant murine cytokines each given intraperitoneally at 50 µg/kg/injection. All treatments induced 30-day survival rates significantly higher than control (survival: 8.3%). 4F (SFT3) and 5F (4F+SDF-1) were the most efficient combinations (81.2% and 87.5%, respectively), which was better than 3F (SFT: 50%), TPO alone (58.3%) and SDF-1 alone (29.2%) and also better than 4F given at 10 µg/kg/injection (4F10: 45.8%) or as a 50 µg/kg single injection at 2 hours (4Fs: 62.5%). Despite delayed mortality occurring mainly from day 150 on and possible long-term hematopoiesis impairment, half of the 30-day protective effect of 4F and 5F was preserved at 300 days. Our results show that short- and long-term survival after irradiation depends on appropriate multicytokine combinations and at optimal concentrations. 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