leukotriene-b4 and Tuberculosis--Meningeal

Topics: Cerebrospinal Fluid; Humans; Leukotriene B4; Receptors, Tumor Necrosis Factor; Treatment Outcome; Tuberculosis, Meningeal; Tumor Necrosis Factor-alpha

To investigate the level of leukotriene B4 (LTB4) in the cerebrospinal fluid (CSF) of patients with tuberculosis meningitis (TBM) and analyze the relationships of LTB4 level with cytological parameters and disease severity.. By ELISA, LTB4 levels were measured in the CSF of the patients with TBM (diagnosed by modified Ziehl-Neelsen staining), cryptococcal meningitis (CM), central nervous system leukemia (CNSL) or non-inflammatory neurological disease (NIND). CSF cytological testing was performed in TBM patients. Disease severity was evaluated by modified Rankin scale (mRS). LTB4 levels were compared between different disease groups, and the relationships of LTB4 level with white blood cell (WBC) counts, neutrophil counts and disease severity were analyzed statistically.. Compared with CM, CNSL or NIND patients, CSF LTB4 level in TBM patients was remarkably higher. CSF LTB4 level in TBM patients was related to neutrophil counts and neutrophil percentages, but not related to WBC counts. No simple linear correlation was found between CSF LTB4 level and disease severity.. CSF LTB4 level in TBM patients can be used as a predictor of inflammation degree, but its relationship with disease severity and prognosis need further exploration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Central Nervous System Neoplasms; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukemia; Leukotriene B4; Male; Meningitis, Cryptococcal; Middle Aged; Nervous System Diseases; Prognosis; Severity of Illness Index; Tuberculosis, Meningeal; Young Adult

Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A(4) hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B(4). We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation.

Topics: Animals; Disease Models, Animal; Humans; Inflammation; Leukotriene A4; Leukotriene B4; Lipoxins; Mitochondria; Mycobacterium Infections; Mycobacterium marinum; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Signal Transduction; Transcription, Genetic; Tuberculosis, Meningeal; Tumor Necrosis Factor-alpha; Zebrafish