Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response.

Abstract

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.

Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

“…TNF-a is present in CSF in neuroinfections and MS [22,23]. Pretreatment of MS and LM CSF with anti-TNF-a MoAb downregulated substantially the ability of these CSF samples to upregulate expression of HLA-DR and CD86 by moDC (Fig.…”

“…TNF-a itself is present in MS patients' CSF and correlates with disease activity [22]. Multiple DC maturation factors, including TNF-a, IL-1b and LPS, are found in CSF in BM [23]. However, in meningitis, the CSF also contains IL-10, a potent DC-down-regulating factor [24], which prevents LPS-induced DC maturation [25] and converts DC into CD14 + macrophage-like cells [26].…”

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

“…In acute inflammatory diseases of the CNS such as viral or bacterial meningitis, IL-6 is elevated in the cerebrospinal fluid (CSF) [45,46]. In Alzheimer's disease, a progressive neurodegenerative disorder of the CNS, local inflammatory reaction may be crucial for the pathogenesis of the disease [47][48][49].…”

Concepts and Mechanisms: Crossing Host Barriers

“…Different bacterial components initiate inflammatory activation of brain endothelial cells, resulting in secretion of cytokines and chemokines such as TNF-a, IL-1, IL-8, or TGF-b, the levels of which are typically elevated in meningitis patients (Waage et al 1989;Fida et al 2006;Nagesh Babu et al 2008). These cytokines may have an autocrine effect on BMEC, leading to increased expression of host receptors that further promote bacterial penetration.…”