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Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1 in cerebrospinal fluid cells in
L M Ossege1, E Sindern, B Voss
1Department of Neurology, Ruhr-University of Bochum, Germany.
Abstract:
Meningitis is an acute inflammatory disease of the pia and arachnoid and the fluid in the subarachnoid space, in which a participation of cytokines can be expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory reactions, transforming growth factor-beta 1 (TGF beta 1) has antagonistic effects and suppresses the inflammation in the subarachnoid space. We investigated the protein concentration and mRNA expression of TNF alpha and TGF beta 1 in cerebrospinal fluid (CSF) by ELISA and intracellularly by non-radioactive in situ hybridization in 23 patients with bacterial or viral meningitis. A higher amount of both cytokines on protein and mRNA level, especially of TNF alpha, could be detected in bacterial infection. While an imbalance of both cytokines with a preponderance of TNF alpha- compared to TGF beta 1-mRNA was visible in CSF cells of patients with bacterial meningitis, a balance of TNF alpha- and TGF beta 1-mRNA or a higher expression of TGF beta 1-mRNA could be detected in viral meningitis. In the acute phase of the disease neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than lymphocytes and monocytes/macrophages, while these cell types were dominating the cytokine synthesis during the healing phase. These data indicate that immunomodulatory mechanisms take place in the CSF compartment itself, regulated by CSF cells in different but specific ways. In addition, TGF beta 1 seems to be involved in the down-regulation of the inflammatory activity and to be one factor in the cytokine network, which could contribute to a lower rate of complications and positive outcomes. Moreover this study favors the possibility to monitor the immunomodulatory mechanisms by non-radioactive in situ hybridization.
Insights
This study reveals that bacterial meningitis shows higher levels of tumor necrosis factor-alpha (TNF alpha) and transforming growth factor-beta 1 (TGF beta 1) compared to viral meningitis. TGF beta 1 may reduce inflammation and improve outcomes in meningitis patients.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Meningitis involves inflammation of the pia, arachnoid, and cerebrospinal fluid (CSF).
- Cytokines, such as TNF alpha (pro-inflammatory) and TGF beta 1 (anti-inflammatory), play a role in meningitis.
- Understanding cytokine dynamics in CSF is crucial for managing meningitis.
Purpose of the Study:
- To investigate the protein concentration and mRNA expression of TNF alpha and TGF beta 1 in CSF.
- To compare these cytokine levels between bacterial and viral meningitis.
- To explore the role of CSF cells in regulating these cytokines during meningitis.
Main Methods:
- Studied 23 patients with bacterial or viral meningitis.
- Measured protein concentration using ELISA.
- Assessed intracellular mRNA expression via non-radioactive in situ hybridization.
Main Results:
- Bacterial meningitis showed higher protein and mRNA levels of both TNF alpha and TGF beta 1, particularly TNF alpha.
- Bacterial meningitis exhibited an imbalance favoring TNF alpha mRNA, while viral meningitis showed a balance or TGF beta 1 dominance.
- Neutrophils were primary cytokine producers in the acute phase, with lymphocytes and macrophages dominating in the healing phase.
Conclusions:
- Immunomodulatory mechanisms occur within the CSF compartment, regulated by CSF cells.
- TGF beta 1 appears to down-regulate inflammation, potentially leading to better outcomes in meningitis.
- Non-radioactive in situ hybridization is a viable method for monitoring immunomodulatory mechanisms in meningitis.