TUMOR-NECROSIS-FACTOR AS A MEDIATOR OF INFLAMMATION IN INFLUENZA-A VIRAL PNEUMONIA

The role of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of influenza A viral pneumonia was examined. CD-1 male mice were challenged intranasally with influenza A virus A/PR/8/34 (H1N1) and administered rabbit anti-mouse TNF alpha-specific-neutralizing antibodies intraperitoneally. The effect of treatment on virus titer, TNF alpha levels, morbidity, mortality, and on pathologic lung lesions were compared with sham-treated controls. The severity of gross and histologic lung lesions positively correlated with the peak bronchoalveolar TNF alpha levels and was ameliorated with anti-TNF alpha treatment. Survivorship was prolonged in mice given a lethal dose of virus by treatment with TNF-alpha neutralizing antibodies. Reduction of TNF alpha levels by treatment with TNF alpha-antibodies did not affect virus titers in the lung. These results suggest that TNF alpha is a mediator of pulmonary inflammation during influenza A viral pneumonia, but may not play a significant anti-viral role in influenza pneumonia. (C) 1995 Academic Press Limited