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Soluble tumor necrosis factor (TNF) receptors conserve TNF bioactivity in meningitis patient spinal fluid
B Möller1, S Ellermann-Eriksen, M Storgaard
1Department of Clinical Immunology, University Hospital of Aarhus, Denmark.
Abstract:
The content of tumor necrosis factor (TNF)-alpha antigen and the bioactivity of soluble TNF receptor type II (sTNF-RII) in cerebrospinal fluid (CSF) from 29 patients with meningeal symptoms and fever were examined. Immunoreactive TNF was demonstrated in CSF from 4 of 7 patients with bacterial meningitis. In 3 of 8 patients with aseptic meningitis, CSF also contained TNF, but TNF bioactivity was confined to samples from patients with bacterial meningitis. Bioactive TNF was exclusively in high-performance liquid chromatography fractions containing 30- to 60-kDa proteins. Lipopolysaccharide induced down-regulation, possibly after shedding of granulocyte surface membrane TNF-RII. Consistently, there was a statistically significant correlation between sTNF-RII and CSF leukocyte counts. Bioactive TNF was found only in CSF containing >1 ng of sTNF-RII/mL; samples without TNF bioactivity contained less sTNF-RII. Thus, a stabilizing effect of sTNF-RII on the oligomeric cytokine in vivo is plausible.
Insights
Tumor necrosis factor (TNF)-alpha antigen and its bioactivity were analyzed in cerebrospinal fluid (CSF) of meningitis patients. Soluble TNF receptor type II (sTNF-RII) correlated with leukocyte counts and stabilized bioactive TNF in bacterial meningitis.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Biochemistry
Background:
- Meningitis involves inflammation of the membranes surrounding the brain and spinal cord.
- Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine implicated in various diseases.
- The role of TNF-alpha and its receptors in the pathogenesis of meningitis requires further elucidation.
Purpose of the Study:
- To investigate the presence and bioactivity of TNF-alpha in cerebrospinal fluid (CSF) of patients with meningeal symptoms.
- To examine the levels and potential role of soluble TNF receptor type II (sTNF-RII) in relation to TNF-alpha bioactivity in CSF.
- To explore the correlation between sTNF-RII, CSF leukocyte counts, and TNF-alpha bioactivity in different types of meningitis.
Main Methods:
- Analysis of TNF-alpha antigen and sTNF-RII bioactivity in CSF samples from 29 patients.
- Detection of immunoreactive TNF using immunoassays.
- Separation and characterization of bioactive TNF using high-performance liquid chromatography (HPLC).
- Correlation analysis between sTNF-RII levels, CSF leukocyte counts, and TNF-alpha bioactivity.
Main Results:
- Immunoreactive TNF was detected in CSF of patients with both bacterial and aseptic meningitis.
- TNF bioactivity was exclusively found in CSF from patients with bacterial meningitis.
- Bioactive TNF was associated with specific protein fractions (30-60 kDa) and required >1 ng/mL of sTNF-RII.
- A significant correlation was observed between sTNF-RII levels and CSF leukocyte counts.
Conclusions:
- sTNF-RII may play a stabilizing role for bioactive TNF in the CSF during bacterial meningitis.
- The presence of sTNF-RII is linked to the inflammatory response in the CSF, as indicated by leukocyte counts.
- These findings suggest a complex interplay between TNF-alpha, sTNF-RII, and inflammation in the context of meningitis.