title: Ciprofloxacin enhances stress erythropoiesis in spleen and increases survival after whole-body irradiation combined with skin-wound trauma.
abstract: Severe hematopoietic loss is one of the major therapeutic targets after radiation-combined injury (CI), a kind of injury resulting from radiation exposure combined with other traumas. In this study, we tested the use of ciprofloxacin (CIP) as a treatment, because of recently reported immunomodulatory effects against CI that may improve hematopoiesis. The CIP regimen was a daily, oral dose for 3 weeks, with the first dose 2 h after CI. CIP treatment improved 30-day survival in mice at 80% compared to 35% for untreated controls. Study of early changes in hematological parameters identified CI-induced progressive anemia by 10 days that CIP significantly ameliorated. CI induced erythropoietin (EPO) mRNA in kidney and protein in kidney and serum; CIP stimulated EPO mRNA expression. In spleens of CI mice, CIP induced bone morphogenetic protein 4 (BMP4) in macrophages with EPO receptors. Splenocytes from CIP-treated CI mice formed CD71⁺ colony-forming unit-erythroid significantly better than those from controls. Thus, CIP-mediated BMP4-dependent stress erythropoiesis may play a role in improving survival after CI.
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland, United States of America.
authors.forename: Risaku
authors.initials: R
authors.lastname: Fukumoto
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland, United States of America.
authors.forename: True M
authors.initials: TM
authors.lastname: Burns
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland, United States of America ; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America ; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Juliann G
authors.initials: JG
authors.lastname: Kiang
mesh_terms: D000740:Anemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D015151:Immunoblotting; D007155:Immunologic Factors / Q000494:pharmacology; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries* / Q000503:physiopathology; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects / Q000528:radiation effects; D016019:Survival Analysis; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D007155:Immunologic Factors; D004921:Erythropoietin; D002939:Ciprofloxacin