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

Abstract

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-␣), 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 ϳ10 6 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.

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

“…In pneumococcal meningitis treatment with a monoclonal antibody to IL-8 given intravenously attenuated the pleocytosis in rabbits. IL-8 plays an important role on the recruitment of neutrophils during experimental pneumococcal meningitis 47 .…”

Chemotactic Factors in Cerebrospinal Fluid during Bacterial Meningitis

“…Although leukocytes within the CSF are important for host defense, it has been demonstrated repeatedly that inhibition of leukocyte recruitment does not necessarily reduce bacterial clearance in the CNS (15,51,82). Altogether, leukocyte accumulation in CSF seems a useful target for additional therapeutic strategies.…”

Algal Polysaccharides, Novel Applications and Outlook

“…Additionally, injection of fucoidan into sensitized mice before hapten challenge can reduce contact hypersensitivity reactions (Nasu et al 1997). Furthermore, recruitment of leukocytes into cerebrospinal fluid in a meningitis model is reduced by fucoidan (Granert et al 1999) as is IL-1 (interleukin-1) production in a similar model (Ostergaard et al 2000).…”