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

114 Scopus citations

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
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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