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
Original language | English |
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Pages (from-to) | 603-608 |
Journal | American journal of respiratory and critical care medicine |
Volume | 155 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1997 |