Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) 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 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). 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-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta 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-alpha and IL-1 beta in the initial events of meningeal inflammation.
Article|
August 01 1990
Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.
O Ramilo,
O Ramilo
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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X Sáez-Llorens,
X Sáez-Llorens
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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J Mertsola,
J Mertsola
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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H Jafari,
H Jafari
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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K D Olsen,
K D Olsen
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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E J Hansen,
E J Hansen
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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M Yoshinaga,
M Yoshinaga
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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S Ohkawara,
S Ohkawara
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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H Nariuchi,
H Nariuchi
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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G H McCracken, Jr
G H McCracken, Jr
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
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O Ramilo
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
X Sáez-Llorens
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
J Mertsola
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
H Jafari
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
K D Olsen
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
E J Hansen
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
M Yoshinaga
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
S Ohkawara
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
H Nariuchi
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
G H McCracken, Jr
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 172 (2): 497–507.
Citation
O Ramilo, X Sáez-Llorens, J Mertsola, H Jafari, K D Olsen, E J Hansen, M Yoshinaga, S Ohkawara, H Nariuchi, G H McCracken; Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.. J Exp Med 1 August 1990; 172 (2): 497–507. doi: https://doi.org/10.1084/jem.172.2.497
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