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Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in

L Tsenova1, A Bergtold, V H Freedman

  • 1Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 13, 1999
PubMed

Insights

Tumor necrosis factor alpha (TNF-alpha) levels in cerebrospinal fluid (CSF) correlate with the severity of tuberculous meningitis. Higher TNF-alpha production by Mycobacterium bovis strains leads to increased pathogenesis in the central nervous system (CNS).

Area of Science:

  • Neuroscience
  • Immunology
  • Infectious Diseases

Background:

  • Tuberculous meningitis pathogenesis is poorly understood.
  • Thalidomide therapy protected rabbits by inhibiting tumor necrosis factor alpha (TNF-alpha) production.
  • Cerebrospinal fluid (CSF) levels of TNF-alpha may correlate with disease severity.

Purpose of the Study:

  • To investigate the correlation between CSF TNF-alpha levels and the pathogenesis of tuberculous meningitis.
  • To compare the virulence of different Mycobacterium bovis strains in the central nervous system (CNS).

Main Methods:

  • Rabbits were infected in the CNS with Mycobacterium bovis Ravenel, M. bovis BCG Pasteur, and M. bovis BCG Montreal.
  • CSF TNF-alpha levels, leukocytosis, protein accumulation, and inflammation were measured.
  • Recombinant BCG strains expressing TNF-alpha were used to assess its role in virulence.

Main Results:

  • M. bovis Ravenel induced the highest TNF-alpha levels, leukocytosis, protein, and inflammation.
  • BCG Montreal was the least virulent strain.
  • Expression of TNF-alpha by BCG Montreal increased its virulence, causing severe meningitis and clinical deterioration.

Conclusions:

  • The level of TNF-alpha produced during mycobacterial CNS infection is a key determinant of pathogenesis.
  • TNF-alpha plays a significant role in the inflammatory response and severity of tuberculous meningitis.

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