Differential release of tumor necrosis factor-alpha from murine peritoneal macrophages stimulated with virulent and avirulent species of mycobacteria

FEMS Immunol Med Microbiol. 1994 Mar;8(3):225-32. doi: 10.1111/j.1574-695X.1994.tb00447.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Assay
  • Cell Division
  • Cells, Cultured
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / microbiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium / cytology
  • Mycobacterium / growth & development
  • Mycobacterium / pathogenicity*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Tumor Necrosis Factor-alpha