Effect of deficiency of tumor necrosis factor alpha or both of its receptors on Streptococcus pneumoniae central nervous system infection and peritonitis

Tumor necrosis factor alpha (TNF-alpha) and TNF-beta are key mediators in b acterial inflammation. We therefore examined the role of TNF-alpha and its two receptors in murine pneumococcal central nervous system infection. TNF- alpha knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)-deficient mice and heterozygous littermates were infected intrace rebrally with a Streptococcus pneumoniae type 3 strain. Mice were monitored until death or were killed 36 h after infection. Bacterial titers in blood , spleen, and brain homogenates were determined. Leukocyte infiltration and neuronal damage were assessed by histological scores. TNF-alpha -deficient mice died earlier than the controls after intracerebral infection although overall survival was similar. TNF-alpha deficiency did not inhibit leukocy te, recruitment into the subarachnoid space and did not lead to an increase d density of bacteria in brain homogenates. However, it caused a substantia l rise of the concentration of S. pneumoniae cells in blood and spleen. Spl een bacterial titers were also increased in p55- and p75-deficient mice. TN F receptor-deficient mice showed decreased meningeal inflammation. Neuronal damage was not affected by either TNF-alpha or TNT receptor deficiency. In a murine model of pneumococcal peritonitis, 10(2) CFU of S. pneumoniae pro duced fatal peritonitis in TNF-alpha -deficient, but not wild-type, mice. E arly leukocyte influx into the peritoneum was impaired in TNF-alpha -defici ent mice. The lack of TNF-alpha or its receptors renders mice more suscepti ble to S. pneumoniae infections.