Tumor necrosis factor α/cachectin and interleukin 1β initiate meningeal inflammation

Octavio Ramilo, Xavier Sáez-Llorens, Jussi Mertsola, Hamid Jafari, Kurt D. Olsen, Eric J. Hansen, Masaru Yoshinaga, Susumu Ohkawara, Hideo Nariuchi, George H. McCracken

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Abstract

Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in the meningeal inflammatory cascade, the results obtained by several groups of investigators 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 IL-1β (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-rrIL-1β, 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 rrIL-1β 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 IL-1β in the initial events of meningeal inflammation.

Original languageEnglish (US)
Pages (from-to)497-507
Number of pages11
JournalJournal of Experimental Medicine
Volume172
Issue number2
Publication statusPublished - Aug 1 1990

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ASJC Scopus subject areas

  • Immunology

Cite this

Ramilo, O., Sáez-Llorens, X., Mertsola, J., Jafari, H., Olsen, K. D., Hansen, E. J., ... McCracken, G. H. (1990). Tumor necrosis factor α/cachectin and interleukin 1β initiate meningeal inflammation. Journal of Experimental Medicine, 172(2), 497-507.