TUMOR NECROSIS FACTOR-ALPHA CACHECTIN AND INTERLEUKIN-1-BETA INITIATE MENINGEAL INFLAMMATION

Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation oftumor necrosis factor α (TNF-α) and interleukin 1β (IL- 1β) in the meningeal inflammatory cascade, the results obtained by several groups ofinvestigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 102-105 IU of purified rabbit TNF-α (RaTNF-α) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant ILlβ (rrIL- 1β). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide- induced meningitis, intracisternal administration of anti-rrlIrlβ, anti-RaTNF-α, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 103 IU of RaTNF-α and 5 ng of rrILlβ resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-α and IL1β in the initial events of meningeal inflammation. © 1990, Rockefeller University Press., All rights reserved.