title: Adjunctive corticosteroid therapy improves lung immunopathology and survival during severe secondary pneumococcal pneumonia in mice.
abstract: Secondary bacterial pneumonia is a significant cause of morbidity and mortality during influenza, despite routine use of standard antibiotics. Antibiotic-induced immunopathology associated with bacterial cell wall lysis has been suggested to contribute to these poor outcomes. Using Streptococcus pneumoniae in a well-established murine model of secondary bacterial pneumonia (SBP) following influenza, we stratified disease severity based on pneumococcal load in the lungs via in vivo bioluminescence imaging. Ampicillin treatment cured mice with mild pneumonia but was ineffective against severely pneumonic mice, despite effective bacterial killing. Adjunctive dexamethasone therapy improved ampicillin-induced immunopathology and improved outcomes in mice with severe SBP. However, early dexamethasone therapy during primary influenza infection impaired lung adaptive immunity as manifest by increased viral titers, with an associated loss of its protective functions in SBP. These data support adjunctive clinical use of corticosteroids in severe cases of community-acquired pneumonia.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Hazem E
authors.initials: HE
authors.lastname: Ghoneim
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000667:Ampicillin; D003907:Dexamethasone
keywords: Antibiotics; Streptococcus pneumoniae; corticosteroids; dexamethasone; immunomodulation; influenza; pneumonia