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

The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte r ecruitment into the cerebrospinal fluid (CSF) during experimental pneumococ cal meningitis. In the present study, the effect of fucoidin treatment on t he release of the proinflammatory cytokines tumor necrosis factor alpha (TN F-alpha), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rab bits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body w eight every second hour starting 4 h after intracisternal inoculation of si milar to 10(6) CFU of Streptococcus pneumoniae type 3 (untreated control gr oup, n = 7), CSF samples were obtained every second hour during a 16-h stud y period, Treatment with fucoidin caused a consistent and significant decre ase 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-alpha levels was observed in the fucoid in-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, Inde ed, there was a significant increase in CSF IL-8 levels (in picograms per m illiliter) 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 sugg est that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-alpha into the CSF during pneumococcal meningi tis, whereas IL-8 may be produced by local cells within the brain.