title: Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice.
abstract: OBJECTIVE
  A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production.
  
  
  METHODS
  Female B6D2F(1)/J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups.
  
  
  RESULTS
  Results demonstrated that the lethal dose for 50% at 30 days (LD(50/30)) of B6D2F(1)/J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection.
  
  
  CONCLUSIONS
  Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required.
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Elliott
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Bolduc
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: G David
authors.initials: GD
authors.lastname: Ledney
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.|b Department of Radiation Biology , F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences , Bethesda , MD , USA.|c Department of Medicine , F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
authors.forename: Juliann G
authors.initials: JG
authors.lastname: Kiang
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Wise
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: Patricia L P
authors.initials: PL
authors.lastname: Romaine
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Newman
authors.affiliation: a Armed Forces Radiobiology Research Institute , Bethesda , MD , USA.|b Department of Radiation Biology , F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D018925:Chemokines / Q000096:biosynthesis; D003311:Cord Factors / Q000008:administration & dosage; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D006133:Growth Substances / Q000096:biosynthesis; D007155:Immunologic Factors / Q000008:administration & dosage*; D064704:Levofloxacin / Q000008:administration & dosage; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D012867:Skin / Q000293:injuries; D014946:Wound Infection / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D018925:Chemokines; D003311:Cord Factors; D016207:Cytokines; D006133:Growth Substances; D007155:Immunologic Factors; D008050:Lipid A; D064704:Levofloxacin; D000658:Amoxicillin; C043399:6,6'-dicorynomycolyl trehalose; C048436:monophosphoryl lipid A
keywords: Anti-microbial therapy; bacterial translocation; chemokines; cytokines; gamma-radiation; immunomodulator; infection; mice; sepsis