Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice

Am J Respir Crit Care Med. 1997 Feb;155(2):603-8. doi: 10.1164/ajrccm.155.2.9032201.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Colony Count, Microbial
  • Female
  • Immunization, Passive*
  • Immunocompromised Host
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism
  • Pneumonia, Pneumococcal / immunology*
  • Pneumonia, Pneumococcal / pathology
  • Streptococcus pneumoniae / isolation & purification
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / physiology*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Peroxidase