title: Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice.
abstract: Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. We sought to determine the role of tumor necrosis factor-alpha (TNF) in the pathogenesis of pneumococcal pneumonia. Induction of pneumonia in C57B1/6 mice by intranasal inoculation with 10(6) colony-forming units (cfu) S. pneumoniae resulted in a sustained increase in TNF activity in lung homogenates reaching a plateau between 12 and 72 h (72 h: 185.49 +/- 54.41 ng/g), while plasma TNF activity remained low or undetectable. Treatment with a neutralizing anti-TNF monoclonal antibody 2 h before inoculation strongly reduced lung TNF activity, but only modestly diminished lung interleukin (IL)-1beta levels, and did not significantly influence lung IL-6, IL-10, and interferon-gamma concentrations. Anti-TNF-treated mice had fourfold more S. pneumoniae cfu isolated from lungs than control mice 40 h after inoculation (p < 0.05), although lung myeloperoxidase activities were similar in both treatment groups. Anti-TNF-treated mice died significantly earlier from pneumococcal pneumonia than control mice (p < 0.05). Endogenously produced TNF is important for host defense during pneumococcal pneumonia.
authors.affiliation: Cornell University Medical College, Department of Surgery, New York, New York 10021, USA.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: C V
authors.initials: CV
authors.lastname: Keogh
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015169:Colony Count, Microbial; D005260:Female; D007116:Immunization, Passive; D016867:Immunocompromised Host; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase