PASSIVE-IMMUNIZATION AGAINST TUMOR-NECROSIS-FACTOR-ALPHA IMPAIRS HOST-DEFENSE DURING PNEUMOCOCCAL PNEUMONIA IN MICE

Streptococcus pneumoniae is the most frequent cause of community-acqui red pneumonia. We sought to determine the role of tumor necrosis facto r-alpha (TNF) in the pathogenesis of pneumococcal pneumonia. Induction of pneumonia in C57B1/6 mice by intranasal inoculation with 10(6) col ony-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 remaine d low or undetectable. Treatment with a neutralizing anti-TNF monoclon al antibody 2 h before inoculation strongly reduced lung TNF activity, but only modestly diminished lung interleukin (IL)-1 beta levels, and did not significantly influence lung IL-6, IL-10, and interferon-gamm a concentrations. Anti-TN F-treated mice had fourfold more S. pneumoni ae cfu isolated from lungs than control mice 40 h after inoculation (p < 0.05), although lung myeloperoxidase activities were similar in bot h treatment groups. Anti-TNF-treated mice died significantly earlier f rom pneumococcal pneumonia than control mice (p < 0.05). Endogenously produced TNF is important for host defense during pneumococcal pneumon ia.