We examined the cerebrospinal fluid (CF) taken on admission from 60 patients with infections caused by Neisseria meningitidis for presence of TNF-alpha, IL-1, and IL-6. TNF-alpha was detected in CF in 55 and 19% (p = 0.03), IL-1 in 50 and 15% (p = 0.05), and IL-6 in 98 and 100% of patients with meningitis and septic shock/bacteremia, respectively. The median IL-6 concentration in CF in patients with meningitis was 154 ng/ml, and in patients with septic shock/bacteremia it was 42 ng/ml (p = 0.001). The level of LPS in CF correlated with the level of TNF-alpha (r = 0.91, p less than 0.001), but not with the level of IL-1 and IL-6. CF levels of TNF-alpha, IL-1, and IL-6 correlated with each other (r = 0.34-0.54, p less than 0.01), with the protein concentration (r = 0.34-0.62, p less than 0.01) and inversely with the CF/blood glucose ratio (r = -0.34 to -0.67, p less than 0.01). Only the Il-6 level correlated with the leukocyte count (r = 0.37, p less than 0.01). In rabbits TNF-alpha, IL-1, and IL-6 activities sequentially appeared in CF within 3 h of injection of meningococcal LPS or viable meningococci, whereas the main infiltration of granulocytes started after 4 h. TNF-alpha was detected in serum at concentrations less than 1/100 of those in CF after administration of LPS into the subarachnoid space, and conversely, TNF-alpha was detected in CF at concentrations 1/100 of those in serum after intravenous injection of LPS. The results demonstrate that TNF-alpha, IL-1, and IL-6 are sequentially produced in the initial phase of the local inflammatory response caused by meningococci, and that the subarachnoid space and systemic circulation are separate compartments with respect to production of TNF-alpha, IL-1, and IL-6.

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