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Infection and Immunity, May 1999, p. 2071-2074, Vol. 67, No. 5
Department of Infectious Diseases, Huddinge
Hospital, S-141 86 Huddinge,1 and
Department of Physiology and Pharmacology, Karolinska
Institutet, S-171 77 Stockholm,2 Sweden, and
Section of Hematology, University Hospital of Trondheim, N-7006
Trondheim, Norway3
Received 14 September 1998/Returned for modification 24 November
1998/Accepted 2 February 1999
The inflammatory response in bacterial meningitis is mediated by
cytokines, such as tumor necrosis factor alpha (TNF-
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Effects of Polysaccharide Fucoidin on Cerebrospinal
Fluid Interleukin-1 and Tumor Necrosis Factor Alpha in Pneumococcal
Meningitis in the Rabbit

) and interleukin-1 (IL-1), which are produced in the subarachnoid space by
different cells, e.g., leukocytes, astrocytes, and microglia. The
recruitment of leukocytes into the cerebrospinal fluid (CSF) has been
shown to contribute to the neurological damage in this disease, a
process which could be enhanced by treatment with antibiotics. In this
study, we have used a rabbit meningitis model for two sets of
experiments with intracisternal (i.c.) injections of
Streptococcus pneumoniae. First, pneumococcal cell wall
(PCW) components were injected i.c., inducing an inflammatory response
with pleocytosis and increased levels of CSF TNF-
) and IL-1 at 6 and
12 h after PCW injection. Treatment with fucoidin, known to
inhibit leukocyte rolling, abolished pleocytosis and inhibited the
release of TNF-
and IL-1. In the second experiment, live
pneumococcal bacteria were injected i.c. and treatment with one dose of
ampicillin (40 mg/kg of body weight intravenously) was given 16 h
after induction of meningitis, causing a sevenfold increase in CSF
leukocytes over a 4-h period. CSF IL-1 levels at 16 h were high
but did not increase further at 20 h. Also, CSF TNF-
levels
were high at 16 h and tended to increase at 20 h. Fucoidin
treatment prevented the antibiotic-induced increase of CSF leukocytes
but had no effect on the TNF-
and IL-1 levels. Taken together,
fucoidin reduced CSF TNF-
and IL-1 levels in acute bacterial
meningitis induced by PCW fragments but had no effect later in the
course of the disease, when live bacteria were used and an inflammatory
increase was caused by a dose of antibiotics.
*
Corresponding author. Mailing address: Department of
Infectious Diseases, Huddinge Hospital, S-141 86 Huddinge, Sweden.
Phone: 46-8-585 80000. Fax: 46-8-585 81916.
Present address: Astra Pain Control AB, Discovery Division, S-141
57 Huddinge, Sweden.
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