Hot on the TRAIL of controlling inflammation in bacterial meningitis
In a study appearing online on June 14 in advance of publication in the July print issue of the Journal of Clinical Investigation, researchers at Charite Universitatsmedizin Berlin report that the molecule known as TRAIL can limit excessive immune responses in bacterial meningitis and as such may be of use to control inflammation of the spinal cord and brain, which causes brain cell death in this life-threatening disease.
Pneumococcal meningitis involves inflammation of the protective membranes covering the brain and spinal cord and is caused by infection with the bacterium Streptococcus pneumoniae. The observed swelling of the brain is largely the result of the excessive immune response to infection. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been previously reported to play a role in the regulation of the host immune response. In the current study, Joerg Weber and colleagues administered components of Streptococcus pneumoniae bacteria to the cerebrospinal fluid bathing the brain and spinal cord of mice lacking TRAIL. They found that these animals suffered from increased inflammation and brain cell death, however these effects were reversed by the administration of recombinant TRAIL (rTRAIL). Importantly, the application of rTRAIL to mice with intact TRAIL and meningitis also decreased inflammation and neuronal cell death. Finally, the authors observed that human patients with bacterial meningitis showed increased synthesis in the cerebrospinal fluid of TRAIL. The results of the study provide evidence that TRAIL acts to limit inflammation of the brain and spinal cord during bacterial meningitis, suggesting that it may be of use as an anti-inflammatory agent in invasive bacterial infections.
TITLE: TRAIL limits excessive host immune responses in bacterial meningitis