Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients.

Abstract

To evaluate the potential role of cachectin/TNF-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of TNF-alpha were determined in cerebrospinal fluid (CSF). After intracerebral, but not systemic, infection with Listeria monocytogenes in mice, TNF-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. However, TNF-alpha was not found in serum during the course of Listeria infection. In contrast to bacterial meningitis, no TNF-alpha was detected at any time in CSF of mice suffering from severe lymphocytic choriomeningitis induced by intracerebral infection with lymphocytic choriomeningitis virus. This difference is striking since both model infections led to a massive infiltration of polymorphonuclear and mononuclear leukocytes into the meninges and CSF. The results found for the two model infections were paralleled by findings in humans; CSF from three out of three patients with bacterial meningitis examined during the first day of hospitalization showed significant levels of TNF-alpha; none of the CSF obtained later than 3 d after hospitalization was positive. In addition, similarly to what was found in mice with viral meningitis, zero out of seven patients with viral meningitis had detectable TNF-alpha in CSF.

Production of B cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients.

“…As shown previously, C5B1/6 mice intracerebrally infected with LCMV showed onset of meningitis 6-7 d after infection and died 6-8 h later (6) . In CSF, white blood cell pleocytosis occurred 6 d after infection, reaching 104 cells/ul on day 7 with 45% mononuclear cells .…”

“…Although originally described as a T cell-derived factor (4), fibroblasts, monocytes, and endothelial cells have also been found to secrete BSF2 (7,11,12). In a previous study on cachectin/TNFa (a product of activated macrophages) it was not possible to identify cachectin/TNF a in CSF of mice with LCMV induced meningitis (6). In contrast, however, cachectin/TNFa was present in CSF of patients with bacterial meningitis or of mice infected intracerebrally with Listeria monocytogenes (6).…”

“…In a previous study on cachectin/TNFa (a product of activated macrophages) it was not possible to identify cachectin/TNF a in CSF of mice with LCMV induced meningitis (6). In contrast, however, cachectin/TNFa was present in CSF of patients with bacterial meningitis or of mice infected intracerebrally with Listeria monocytogenes (6). In viral meningitis, the BSF2 in CSF of patients with aseptic viral meningitis and HSV1-induced encephalitis .…”

Cytotoxic T Lymphocyte Control of Acute Lymphocytic Choriomeningitis Virus Infection: Interferon , but Not Tumour Necrosis Factor , Displays Antiviral Activity in vivo

“…Furthermore we found no evidence that combined treatment of recombinant TNF~ and IFN-y enhance virus elimination over that associated with IFN-~, alone (Table 5). The absence of any antiviral activity of exogenous TNF~ during acute LCMV infection, together with the absence of TNF~ activity in the cerebrospinal fluid of mice with acute lymphocytic choriomeningitis, in which mononuclear infiltration is extensive (Leist et al, 1988), suggest that TNF does not play a significant role in the control of acute LCMV infection.…”

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis

“…As TNF-␣, a cytokine mainly produced by activated monocytes/ macrophages, is one of major mediators of bacterial meningitis (7,28,29), and bacterial DNA and CpG ODN is known to stimulate macrophages to release TNF-␣ (12), we assessed its impact on the course of meningitis. We collected CSF samples from SD rats injected with CpG ODN and analyzed TNF-␣ in CSF by ELISA.…”