TNF-α, IL-1β, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae

Abstract

Bacterial meningitis caused by Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae, including sensory-motor deficits, seizures, and impairment of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, were shown to contribute to the development of brain injury in bacterial meningitis. Thus, the aim of this study was to verify the levels of the TNF-alpha, IL-1beta, IL-6, and CINC-1 in the rat brain after pneumococcal meningitis. The animals underwent a magna cistern tap receiving either 10 microL of sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration of 5x10(9) cfu/mL. The placebo group was killed immediately after the induction and the meningitis group at 0, 6, 12, 24, 48, and 96h after induction. The brains were removed followed by the isolation of the hippocampus and prefrontal cortex for determining TNF-alpha, IL-1beta, IL-6, and CINC-1 levels. In the hippocampus we found increased levels of the TNF-alpha only at 6h (p<0.01; F=3.777); CINC-1 levels increased at 6 and 24h (p<0.001; p<0.05; F=15.05); and IL-6 and IL-1beta levels were not altered. In the prefrontal cortex, the TNF-alpha levels were found to be increased only at 6h (p<0.05; F=4.921); IL-6 (p<0.05; F=11.69) and IL-1beta (p<0.001; F=132.0) levels were found to be increased only at 24h after meningitis induction; and CINC-1 levels were found to be increased at 6, 12, and 24h (p<0.01; p<0.01; p<0.01; F=16.86) after meningitis induction. Our data suggest that cytokine/chemokine levels can be putative biomarkers of brain damage in the first hours of the pneumococcal meningitis.

Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis

“…In a further study, TNFa level in hippocampus, frontal cortex, and CSF were increased, confirming the deleterious effect of TNFa on the brain tissue [30]. It has been also observed that infecting microglia-mixed cultures with L. monocytogenes, increased the MCP-1 and TNF-a levels and reduced levels of IFN-a/b concomitant with a bad prognosis of listeriosis and neuronal destruction by apoptosis [10].…”

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

“…In patients suffering from bacterial meningitis, cerebrospinal fluid levels of caspase-1 were increased (258). In children with bacterial meningitis, as well as a rat model of pneumococcal meningitis, increased IL-1␤ levels were measured in the CSF (30,86). Koedel et al showed that mice lacking caspase-1 displayed less severe inflammation and improved survival in a pneumococcal meningitis mouse model (258).…”

“…GRO-␣ was also found at high levels in the CSF of patients with bacterial meningitis (553), as well as in a rat model of pneumococcal meningitis, but it did not exert any chemotactic activity (30,553 …”

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

“…TNF-α leads to NF-κB activation in the CSF and brain resident cells, which regulates the expression of many pro-inflammatory mediators 29 . In animal models for pneumococcal meningitis, TNF-α was produced in the first 6 h of the immune response 30 . Intrathecal administration of TNF-α results in a similar pathophysiological characteristic of bacterial meningitis such as BBB disruption, facilitating bacterial traversal into the CSF 31 , on the other hand, TNF-α deficient mice increased mortality and spatial memory deficits 32 .…”

“…IL-1β has potent stimulatory effects on granulocytes white cells; it promotes the adhesion of neutrophils and monocytes in endothelial cells 33 . IL-1β is found in the CSF of patients with bacterial meningitis 34 , furthermore, in animal models it was produced in the first 24 h after pneumococcal meningitis induction 30 , although intrathecal administration of IL-1β did not lead to CSF pleocytosis or brain edema 35 . However, the mortality was significantly higher and earlier in the course of the disease among IL-1 receptor (IL-1R) gene-deficient mice, demonstrating that endogenous IL-1β is required for an adequate host defense in pneumococcal meningitis 36 .…”