{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:38Z","timestamp":1785428078404,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AAI-12044-001-04000"],"award-info":[{"award-number":["AAI-12044-001-04000"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"award":["AAI-12044-001-04000"],"award-info":[{"award-number":["AAI-12044-001-04000"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"AFRRI Intramural funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Widespread uses of nuclear materials increase the risk of accidental or intentional radiation exposure, which can result in acute radiation syndrome (ARS). Hematopoietic ARS (H-ARS) occurs at relatively low doses and is potentially lethal without intervention. While several FDA-approved cytokine-based radiomitigators exist, many require repeated dosing, complicating deployment in mass-casualty scenarios. This study evaluated a novel long-acting, murine-reactive granulocyte\u2013macrophage colony-stimulating factor (LA-GM-CSF; mPDM608) as a prophylactic and mitigative countermeasure for H-ARS. Male and female C57BL\/6 mice were exposed to lethal or sublethal total body irradiation (TBI) and treated with LA-GM-CSF using single- or multi-dose regimens administered before or after TBI. Safety, 30-day survival, hematologic recovery, bone marrow cellularity, serum GM-CSF pharmacokinetics, endothelial injury markers, and cytokine profiles were assessed using standard hematology, histopathology, ELISA, and multiplex assays. LA-GM-CSF was well tolerated at doses up to 30 mg\/kg. Single or limited dosing conferred significant survival benefits compared with vehicle controls, with optimal efficacy observed at lower doses (3 mg\/kg). Post-TBI administration as a single dose 24 h after exposure markedly improved survival in both sexes, with stronger hematopoietic recovery in males. LA-GM-CSF accelerated recovery of neutrophils, red blood cells, platelets, hematocrit, and sternal megakaryocytes, prolonged circulating GM-CSF levels, and favorably modulated endothelial injury markers and select cytokines. LA-GM-CSF demonstrates strong potential as a next-generation radiation countermeasure, providing robust survival benefit and hematopoietic recovery with minimal dosing. The results shown here support further development for H-ARS management under the FDA Animal Rule.<\/jats:p>","DOI":"10.3390\/ijms27094147","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:03:37Z","timestamp":1778144617000},"page":"4147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LA-GM-CSF, a Long-Acting Cytokine Mitigates and Prevents H-ARS Mediated Lethality in Mice Exposed to Total Body Gamma Radiation"],"prefix":"10.3390","volume":"27","author":[{"given":"Gregory P.","family":"Holmes-Hampton","sequence":"first","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylee","family":"Valenzia","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-7640","authenticated-orcid":false,"given":"Vidya P.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA"},{"name":"Henry M. Jackson Foundation for Advancement of Military Medicine, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkateshwara Rao","family":"Dronamraju","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA"},{"name":"Henry M. Jackson Foundation for Advancement of Military Medicine, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Woods","sequence":"additional","affiliation":[{"name":"Calibr, a Division of Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean B.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Calibr, a Division of Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0261-460X","authenticated-orcid":false,"given":"Sanchita P.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","unstructured":"International Atomic Energy Agency (2023). 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