Effects of polysaccharide fucoidin on cerebrospinal fluid interleukin-1 and tumor necrosis factor alpha in pneumococcal meningitis in the rabbit

The inflammatory response in bacterial meningitis is mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), which are produced in the subarachnoid space by different cells, e.g. leuko cytes, astrocytes, and microglia, The recruitment of leukocytes into the ce rebrospinal fluid (CSF) has been shown to contribute to the neurological da mage in this disease, a process which could be enhanced by treatment with a ntibiotics, In this study, we have used a rabbit meningitis model for two s ets of experiments with intracisternal (i.c.) injections of Streptococcus p neumoniae. First, pneumococcal cell wall (PCW) components were injected i.c ., inducing an inflammatory response with pleocytosis and increased levels of CSF TNF-alpha and IL-1 at 6 and 12 h after PCW injection, Treatment with fucoidin, known to inhibit leukocyte rolling, abolished pleocytosis and in hibited the release of TNF-alpha and IL-1. In the second experiment, live p neumococcal bacteria were injected i.c. and treatment with one dose of ampi cillin (40 mg/kg of body weight intravenously) was given 16 h after inducti on 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-alpha levels were high at 16 h and tended to increase a t 20 h, Fucoidin treatment prevented the antibiotic-induced increase of CSF leukocytes but had no effect on the TNF-alpha and IL-1 levels. Taken toget her, fucoidin reduced CSF TNF-alpha and IL-1 levels in acute bacterial meni ngitis induced by PCW fragments but had no effect later in the course of th e disease, when live bacteria were used and an inflammatory increase was ca used by a dose of antibiotics.