title: Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology, and Survival in the Mouse Model of Bubonic Plague.
abstract: Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague.
  
  
  
  Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-Y. pestis antibodies alone or in combination with the corticosteroid methylprednisolone.
  
  
  
  The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase 9 in the tissues, and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs.
  
  
  
  Corticosteroids induce an unexpectedly effective antibacterial response apart from their antiinflammatory properties, thereby improving treatment efficacy.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Vagima
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Avital
authors.initials: A
authors.lastname: Tidhar
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Zauberman
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Moshe
authors.initials: M
authors.lastname: Aftalion
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: David
authors.initials: D
authors.lastname: Gur
authors.affiliation: Surgeon General Headquarters, IDF Medical Corps, Tel Hashomer, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Fogel
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Theodor
authors.initials: T
authors.lastname: Chitlaru
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Flashner
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona.
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Mamroud
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage*; D058491:Bacterial Load; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D008168:Lung / Q000473:pathology; D008775:Methylprednisolone / Q000008:administration & dosage*; D051379:Mice; D010930:Plague / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D007155:Immunologic Factors; D008775:Methylprednisolone
keywords: Y. pestis; anti-F1; anti-LcrV; antibodies; corticosteroids; methylprednisolone; passive therapy; plague