Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza.
Mortality after influenza is often due to secondary bacterial pneumonia with Streptococcus pneumoniae, particularly in the elderly. The reasons for the high fatality rate seen with this disease are unclear. To further characterize the pathogenesis of pneumonia after influenza in a mouse model, we examined the pathology and immunology that leads to fatal infection. Influenza-infected mice were either euthanized 24 h after secondary infection with S. pneumoniae for determination of pathology, bacterial cultures, and levels of immune effectors or were followed by use of a live imaging system for development of pneumonia. Influenza-infected mice challenged with each of 3 serotypes of pneumococcus developed a severe, necrotic pneumonia and met endpoints for euthanasia in 24 to 60 h. Strikingly elevated levels of both pro- and anti-inflammatory molecules including interleukins 6 and 10, macrophage inflammatory protein 1alpha, and chemokine KC were present in the blood. High levels of these cytokines and chemokines as well as tumor necrosis factor alpha, interleukin 1beta, and heme oxygenase 1 were present in the lungs, accompanied by a massive influx of neutrophils. Mortality correlated with the development of pneumonia and lung inflammation but not with bacteremia. This model has the potential to help us understand the pathogenesis of severe lung infections.
Smith
Matthew W
MW
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
Schmidt
Jeffrey E
JE
Rehg
Jerold E
JE
Orihuela
Carlos J
CJ
McCullers
Jonathan A
JA
D000818:Animals; D018893:Bronchoalveolar Lavage; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007251:Influenza, Human / Q000150:complications*; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011018:Pneumonia, Pneumococcal / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D013296:Streptococcus pneumoniae; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051547:Heme Oxygenase-1