Microbiological and inflammatory factors associated with the development of pneumococcal pneumonia.
Pneumococcal pneumonia still is associated with a high mortality rate, despite appropriate antimicrobial therapy. Many gaps remain in the understanding of the pathogenesis of this deadly infection. The microbial and inflammatory events that characterize survival or death after intranasal inoculation of mice with an LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was associated with rapid bacterial clearance and low inflammation (surfactant and red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury was noted. By contrast, death was preceded by strong bacterial growth that peaked 48 h after the infection and was associated with gradual increases in pulmonary levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2, monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.
Dallaire
F
F
Centre de Recherche en Infectiologie, Université Laval, Québec City, Québec, Canada. frederic.dallaire@crchul.ulaval.ca
Ouellet
N
N
Bergeron
Y
Y
Turmel
V
V
Gauthier
M C
MC
Simard
M
M
Bergeron
M G
MG
D000818:Animals; D000917:Antibody Formation; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018932:Chemokine CCL2 / Q000032:analysis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000032:analysis; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D007249:Inflammation; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D051379:Mice; D015846:Monokines / Q000032:analysis; D009504:Neutrophils / Q000502:physiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha