COMBINATION OF THALIDOMIDE PLUS ANTIBIOTICS PROTECTS RABBITS FROM MYCOBACTERIAL MENINGITIS-ASSOCIATED DEATH

Tuberculous meningitis (TBM) is a devastating form of tuberculosis tha t 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 leukocyt osis (predominantly mononuclear cells), high protein levels, and relea se of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal f luid within 1 day. Histologically, severe meningitis with thickening o f the leptomeninges, prominent vasculitis, and encephalitis was appare nt, and mortality was 75% by day 8. In animals treated with antituberc ulous antibiotics only, the inflammation and lesions of the brain pers isted despite a decrease in mycobacteria; 50% of the rabbits died. Whe n thalidomide treatment was combined with antibiotics, there was a mar ked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived , suggesting a potential clinical use for thalidomide in TBM.