title: The role played by tumor necrosis factor during localized and systemic infection with Streptococcus pneumoniae.
abstract: Tumor necrosis factor (TNF) has been proposed as a major mediator of host resistance in murine models of Streptococcus pneumoniae infection; in humans, anti-TNF therapies have been implicated in increased susceptibility to pneumococcal infection. Here, we use nonlethal (serotype 6B) and lethal (serotype 3) S. pneumoniae, neutralizing monoclonal antibodies to TNF, and TNF gene-deficient mice to reexamine the role played by TNF in antistreptococcal responses. After nonlethal challenge, primary resistance and all examined parameters of the cellular inflammatory response occurred independently of TNF activity. After lethal challenge, TNF deficiency resulted in more-rapid death but did not affect lung inflammation. However, the livers of the TNF gene-deficient mice, but not of the control mice, exhibited extensive signs of systemic disease. TNF, therefore, is dispensable for a complete cellular pulmonary inflammatory response to S. pneumoniae infection but enhances survival from disseminated lethal infection, at least in part by delaying systemic organ damage.
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. ak510@york.ac.uk
authors.forename: Alun C
authors.initials: AC
authors.lastname: Kirby
authors.forename: John G
authors.initials: JG
authors.lastname: Raynes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D000818:Animals; D008168:Lung / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D010586:Phagocytes / Q000502:physiology; D011008:Pneumococcal Infections / Q000097:blood / Q000503:physiopathology*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha