Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone

Significance Despite appropriate antibiotic treatment, tuberculous meningitis carries a high mortality ascribed to overexuberant inflammation. Genetic variations in the enzyme, LTA4H, alter inflammation, with individuals carrying the inflammation-associated LTA4H variant benefitting from antiinflammatory steroids administered alongside antibiotics. A prior study found poor correlation between LTA4H genotype and cerebrospinal fluid levels of cytokines, key mediators of inflammation. The study used “frequentist” statistical methods that can fail to detect true differences. Using Bayesian statistics, which can detect significant differences not found by frequentist methods, we found good correlation between LTA4H genotype and cytokine levels, and cytokine levels and outcome even independent of LTA4H genotype. These findings suggest that LTA4H and additional inflammation factors affect outcome and suggest tailoring steroid therapy to cytokine levels.