title: Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses.
abstract: OBJECTIVE
  Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities.
  
  
  METHODS
  Prospective, randomized controlled study.
  
  
  METHODS
  Animal laboratory in a university medical center.
  
  
  METHODS
  Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple time points.
  
  
  RESULTS
  The host response was dependent on the causative organism as well as kinetics of mortality, but the pro-inflammatory and anti-inflammatory responses were independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of five distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary macrophage inflammatory peptide-2 and interleukin-10 with progression of infection, whereas elevated plasma tumor necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of fulminant disease with >90% mortality within 48 hrs.
  
  
  CONCLUSIONS
  Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a potential therapeutic approach in the treatment of sepsis.
authors.affiliation: Departments of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: McConnell
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: McDunn
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Clark
authors.forename: W Michael
authors.initials: WM
authors.lastname: Dunne
authors.forename: David J
authors.initials: DJ
authors.lastname: Dixon
authors.forename: Isaiah R
authors.initials: IR
authors.lastname: Turnbull
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dipasco
authors.forename: William F
authors.initials: WF
authors.lastname: Osberghaus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sherman
authors.forename: James R
authors.initials: JR
authors.lastname: Martin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walter
authors.forename: J Perren
authors.initials: JP
authors.lastname: Cobb
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Buchman
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hotchkiss
authors.forename: Craig M
authors.initials: CM
authors.lastname: Coopersmith
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions / Q000276:immunology / Q000502:physiology*; D018836:Inflammation Mediators / Q000097:blood; D007958:Leukocyte Count; D051379:Mice; D008815:Mice, Inbred Strains; D009195:Peroxidase / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology* / Q000401:mortality; D011336:Probability; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D011897:Random Allocation; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase