EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN CEREBROSPINAL-FLUID CELLS IN MENINGITIS

Meningitis is an acute inflammatory disease of the pia and arachnoid a nd the fluid in the subarachnoid space, in which a participation of cy tokines can be expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory reactions, transforming growth factor-beta 1 (T GF 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 (C SF) by ELISA and intracellularly by non-radioactive in situ hybridizat ion in 23 patients with bacterial or viral meningitis. A higher. amoun t of both cyto,Lines on protein and mRNA level. especially of TNF alph a, could be detected in bacterial infection. While an imbalance of bot h cytokines with a preponderance of TNF alpha-compared to TGF beta 1-m RNA 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 TG F beta 1-mRNA could be detected in viral meningitis. In the acute phas e of the disease neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than lymphocytes and monocytes/macrophages, while the se cell types were dominating the cytokine synthesis during the healin g phase. These data indicate that immunomodulatory mechanisms take pla ce 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 compli cations and positive outcomes. Moreover this study favors the possibil ity to monitor the immunomodulatory mechanisms by non-radioactive in s itu hybridization.