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Infection and Immunity, June 2000, p. 3153-3157, Vol. 68, No. 6
Division of Microbiology, Department of
Research and Development, Statens Serum
Institut,1 and Department of
Infectious Diseases, Hvidovre University
Hospital,2 Copenhagen, Denmark
Received 5 November 1999/Returned for modification 25 January
2000/Accepted 29 February 2000
The polysaccharide fucoidin is a selectin blocker that inhibits
leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect
of fucoidin treatment on the release of the proinflammatory cytokines
tumor necrosis factor alpha (TNF-
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Inhibition of Leukocyte Entry into the Brain by the
Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but
Increases IL-8 Levels in Cerebrospinal Fluid during Experimental
Pneumococcal Meningitis in Rabbits
), interleukin-1 (IL-1), and IL-8
into the CSF was investigated. Rabbits (n = 7) were
treated intravenously with 10 mg of fucoidin/kg of body weight every
second hour starting 4 h after intracisternal inoculation of
~106 CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were
obtained every second hour during a 16-h study period. Treatment with
fucoidin caused a consistent and significant decrease in CSF IL-1
levels (in picograms per milliliter) between 12 and 16 h (0 versus
170, 0 versus 526, and 60 versus 1,467, respectively;
P < 0.02). A less consistent decrease in CSF TNF-
levels was observed in the fucoidin-treated group, but with no
significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels.
Indeed, there was a significant increase in CSF IL-8 levels (in
picograms per milliliter) in the fucoidin-treated group at 10 and
12 h (921 versus 574 and 1,397 versus 569, respectively;
P < 0.09). In conclusion, our results suggest that
blood-derived leukocytes mainly are responsible for the release of IL-1
and to some degree TNF- into the CSF during pneumococcal meningitis,
whereas IL-8 may be produced by local cells within the brain.
*
Corresponding author. Mailing address: Division of
Microbiology, Department of Research and Development, Statens Serum
Institut, Artillervej 5, DK-2300 Copenhagen S, Denmark. Phone: 45 32688208. Fax: 45 32683887. E-mail: coa{at}ssi.dk.
Infection and Immunity, June 2000, p. 3153-3157, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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