Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection,
characterized by a dysregulated immune response that frequently leads to neurologic
injury and death despite the best available treatment. The mechanisms driving the
inflammatory response in TBM are not well understood. To gain insights into these
mechanisms, we used a lipid mediator–profiling approach to investigate the
regulation of a novel group of host protective mediators, termed specialized
proresolving mediators (SPMs), in the cerebrospinal fluid (CSF) of adults with TBM.
Herein, using CSF from patients enrolled into a randomized placebo-controlled trial
of adjunctive aspirin treatment, we found distinct lipid mediator profiles with
increasing disease severity. These changes were linked with an up-regulation of
inflammatory eicosanoids in patients with severe TBM and a decrease in the production
of a number of SPMs. CSF proresolving mediator concentrations were also associated
with 80-d survival. In survivors, we found a significant increase in proresolving
mediator concentrations, including the lipoxygenase 5–derived 13-series
resolvin (RvT)2, RvT4, and 15-epi-lipoxin B4, compared with those who
died. Of note, treatment of patients with high-dose aspirin led to a decrease in the
concentrations of the prothrombic mediator thromboxane A2, reduced brain
infarcts, and decreased death in patients with TBM. Together, these findings identify
a CSF SPM signature that is associated with disease severity and 80-d mortality in
TBM.—Colas, R. A., Nhat, L. T. H., Thuong, N. T. T., Gómez, E. A., Ly,
L., Thanh, H. H., Mai, N. T. H., Phu, N. H., Thwaites, G. E., Dalli, J. Proresolving
mediator profiles in cerebrospinal fluid are linked with disease severity and outcome
in adults with tuberculous meningitis.