A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-Associated death

Liana Tsenova, Karen Sokol, Victoria H. Freedman, Gilla Kaplan

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-α (TNF-α) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-α levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.

Original languageEnglish (US)
Pages (from-to)1563-1572
Number of pages10
JournalJournal of Infectious Diseases
Volume177
Issue number6
StatePublished - 1998
Externally publishedYes

Fingerprint

Meningeal Tuberculosis
Thalidomide
Meningitis
Leukocytosis
Encephalitis
Anti-Bacterial Agents
Rabbits
Tumor Necrosis Factor-alpha
Central Nervous System Infections
Mycobacterium
Mycobacterium bovis
Vasculitis
Cerebrospinal Fluid
Tuberculosis
Pathology
Mortality
Brain
Therapeutics
Proteins

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-Associated death. / Tsenova, Liana; Sokol, Karen; Freedman, Victoria H.; Kaplan, Gilla.

In: Journal of Infectious Diseases, Vol. 177, No. 6, 1998, p. 1563-1572.

Research output: Contribution to journalArticle

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