Cytokine-based treatment of accidentally irradiated victims and new approaches  Francis Hérodin, Michel Drouet  Experimental Hematology  Volume 33, Issue 10, Pages 1071-1080 (October 2005) DOI: 10.1016/j.exphem.2005.04.007 Copyright © 2005 International Society for Experimental Hematology Terms and Conditions

Figure 1 Spontaneous recovery of neutrophil (ANC) and platelet (PLT) counts in 7-Gy total body irradiation (TBI) 60Co gamma-irradiated monkeys (n = 5). Experimental Hematology 2005 33, 1071-1080DOI: (10.1016/j.exphem.2005.04.007) Copyright © 2005 International Society for Experimental Hematology Terms and Conditions

Figure 2 Response of the stem cell niche to irradiation: immaturity-related cell radiosensitivity and cell–cell and cell–matrix interactions as key parameters for hematopoietic recovery. The stem cell niche constitutes a functional unit that responds to irradiation as a whole, since all components (in particular hematopoietic stem cells [HSC], stromal cells, osteoblasts) interact with each other (including bystander effects) within the extracellular matrix, which can be considered as a tridimensional gradient of cytokines and chemokines. Thus, postirradiation recovery of intrinsically radioresistant HSC depends on nonhematopoietic stromal cell integrity. However, the nonuniform pattern of radiation dose distribution in nuclear/radiological accident settings has a significant impact on damage and subsequent reconstitution potential. Stromal cell dependence of hematopoietic cells decreases as the latter mature. Moreover, little is known about the contribution of circulating HSPC to recovery. Experimental Hematology 2005 33, 1071-1080DOI: (10.1016/j.exphem.2005.04.007) Copyright © 2005 International Society for Experimental Hematology Terms and Conditions

Figure 3 New approaches to treatment strategy for hematopoietic syndrome (Grades H2 and H3 of METREPOL score [63]) depending on time after radiation exposure. The medical management of acute radiation syndrome (ARS) should take damage kinetics into account. Apoptotic precocity makes it necessary to shorten the delay between irradiation and treatment time. Early administration of cytokines is recommended to prevent hematopoietic stem and progenitor cells (HSPC) and stromal cell death. Cytokine treatment would also stimulate intrinsically radioresistant stem cells and preserved progenitors in order to recapitulate myelopoiesis and lymphopoiesis. Beyond bone marrow radiation injury, ARS should be considered to be a global illness. Locally, hematopoietic niche disorders may account for partial long-term recovery. New agents under development could mitigate these disorders. At whole-body level, a durable inflammatory process leading to the development of multiple organ dysfunction syndrome (MODS), should be counteracted by using appropriate drugs such as steroids, NSAIDs, cytokine antagonists, antioxidants, antifibrotic, antimicrobial, and antiviral agents. Experimental Hematology 2005 33, 1071-1080DOI: (10.1016/j.exphem.2005.04.007) Copyright © 2005 International Society for Experimental Hematology Terms and Conditions