title: Ciprofloxacin modulates cytokine/chemokine profile in serum, improves bone marrow repopulation, and limits apoptosis and autophagy in ileum after whole body ionizing irradiation combined with skin-wound trauma.
abstract: Radiation combined injury (CI) is a radiation injury (RI) combined with other types of injury, which generally leads to greater mortality than RI alone. A spectrum of specific, time-dependent pathophysiological changes is associated with CI. Of these changes, the massive release of pro-inflammatory cytokines, severe hematopoietic and gastrointestinal losses and bacterial sepsis are important treatment targets to improve survival. Ciprofloxacin (CIP) is known to have immunomodulatory effect besides the antimicrobial activity. The present study reports that CIP ameliorated pathophysiological changes unique to CI that later led to major mortality. B6D2F1/J mice received CI on day 0, by RI followed by wound trauma, and were treated with CIP (90 mg/kg p.o., q.d. within 2 h after CI through day 10). At day 10, CIP treatment not only significantly reduced pro-inflammatory cytokine and chemokine concentrations, including interleukin-6 (IL-6) and KC (i.e., IL-8 in human), but it also enhanced IL-3 production compared to vehicle-treated controls. Mice treated with CIP displayed a greater repopulation of bone marrow cells. CIP also limited CI-induced apoptosis and autophagy in ileal villi, systemic bacterial infection, and IgA production. CIP treatment led to LD(0/10) compared to LD(20/10) for vehicle-treated group after CI. Given the multiple beneficial activities of CIP shown in our experiments, CIP may prove to be a useful therapeutic drug for CI.
authors.affiliation: Radiation Combined Injury Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Risaku
authors.initials: R
authors.lastname: Fukumoto
authors.forename: Lynnette H
authors.initials: LH
authors.lastname: Cary
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Gorbunov
authors.forename: Eric D
authors.initials: ED
authors.lastname: Lombardini
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Elliott
authors.forename: Juliann G
authors.initials: JG
authors.lastname: Kiang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002939:Ciprofloxacin / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D012867:Skin / Q000293:injuries*; D014916:Whole-Body Irradiation; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D002939:Ciprofloxacin