title: Differential release of tumor necrosis factor-alpha from murine peritoneal macrophages stimulated with virulent and avirulent species of mycobacteria.
abstract: The ability of Mycobacterium tuberculosis H37Rv and H37Ra, M. bovis BCG and M. smegmatis to induce the secretion of tumor necrosis factor-alpha (TNF-alpha) by cultured murine peritoneal macrophages is inversely related to their virulence. The avirulent species of mycobacteria which were unable to persist in macrophages were capable of inducing significant levels of TNF-alpha compared to that formed in cultures infected with the virulent M. tuberculosis H37Rv. This difference was also associated with an inherent toxicity by live H37Rv for macrophage cultures. Heat-killed H37Rv was non-toxic and induced significant levels of TNF-alpha; in contrast, live and heat-killed suspensions of avirulent mycobacteria had an equivalent ability to trigger TNF-alpha secretion. The TNF-alpha response was dose-dependent, related directly to the percentage of infected cells, and peaked 6-12 h post-infection. An early and vigorous TNF-alpha response appears to be a marker of macrophage resistance, while the downregulation of this response seems associated with macrophage toxicity and unrestricted mycobacterial growth.
authors.affiliation: Institute of Medicine and Public Health, University of Pavia, Varese, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Falcone
authors.forename: E B
authors.initials: EB
authors.lastname: Bassey
authors.forename: A
authors.initials: A
authors.lastname: Toniolo
authors.forename: P G
authors.initials: PG
authors.lastname: Conaldi
authors.forename: F M
authors.initials: FM
authors.lastname: Collins
mesh_terms: D000818:Animals; D001681:Biological Assay; D002455:Cell Division; D002478:Cells, Cultured; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000166:cytology / Q000254:growth & development / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha