title: Effects of minocycline on hematopoietic recovery after whole-body irradiation.
abstract: OBJECTIVE
  We previously found that minocycline enhanced the levels of several leukocyte populations and had the capacity to induce secretion of certain cytokines early after irradiation. In the current study we further determined the drug's effect on hematopoietic recovery.
  
  
  METHODS
  Minocycline was injected intraperitoneally into C57BL/6 mice for 5 days, beginning immediately before exposure to (60)Co γ-rays (1, 2, 3 Gy). Thirty-two days post-irradiation, spleen and blood were collected to quantify cell populations, cytokines in splenic T-cell supernatants after anti-CD3 activation, and chromosomic status based on spectral karyotyping.
  
  
  RESULTS
  While radiation resulted in significantly lower B-cell counts at 3 Gy in both blood and spleen, minocycline treatment increased the counts and/or percentages of splenic B-cells at 2 Gy and 3 Gy. In spleen supernatants, the drug-alone increased the levels of cytokines, including interleukin-1α (IL-1α) and IL-6 that are radioprotective, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF that accelerate neutrophil recovery. In addition, minocycline suppressed the production of interferon-γ that can prevent hematopoiesis. Dose-dependent radiation-induced chromosomic abnormalities were present in splenic leukocytes.
  
  
  CONCLUSIONS
  The data indicate that minocycline exerts a relatively long-term effect on parameters that influence hematopoietic recovery. Further testing of this drug as a countermeasure for acute radiation syndrome, is necessary to determine its full potential.
authors.affiliation: Department of Basic Sciences, Divisions of Biochemistry and Microbiology, Loma Linda University and Medical Center, Loma Linda, CA 92354, USA. dgridley@dominion.llumc.edu
authors.forename: Shalini
authors.initials: S
authors.lastname: Mehrotra
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D001772:Blood Cell Count; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects*; D007274:Injections, Intraperitoneal; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D032681:Spectral Karyotyping; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008911:Minocycline