The Research Of Relationship Between Leukotriene Metabolism Pathway And Tuberculous Meningitis

Leukotriene metabolism pathway is a critical step in the inflammation response of host against bacterial, and the products of this pathway, including LXA4、LTA4 and LTB4 all participate in this process. According the research from the zebra fish-Mycobacterium marinum model, LTB4 play a critical role in the host against tuberculosis and especially the LTA4 h gene polymorphism is closely related to the susceptibility and prognosis of Glucocorticoid treatment in tuberculosis diseases. But there were some controversies about the role of LTA4 h in the Tuberculous Meningitis. Whether the SNP of LTA4 H can direct the adjunctive therapy in the TBM patients should be clarified.Objective:To measure the LTA4 H polymorphism and the levels of CSF LTB4 and to investigate the relationship between the leukotriene metabolism pathway and the clinical data、inflammation response and prognosis.Method:The research can be divided into three parts. Firstly 119 TBM patients with definite diagnosis were retrospective investigated and their clinical materials including the clinical manifestation and the CSF pressure、protein and immunoglobulin and prognosis. Secondly, the definite TBM patients with Informed consent were included and the gene polymorphisms of LTA4 H were detected. The relationship between the SNP of LTA4 H and the disease severity and prognosis were also analyzed. Thirdly the 32 TBM patients with definite diagnosis without anti-TB treatment were included and level of CSF LTB4 was measured in the first 72 hours when they were admitted to our hospital. The relationship between the level of CSF LTB4 and the prognosis CSF cytology and protein were analyzed. The enumeration data was expressed as percent(%) and the quantitative data was expressed as()。 The relationship between glucocorticoid treatment and these records were further analyzed by GraphPad Prism 5 software.Results:1.119 TBM patients with definite diagnosis were enrolled in this study, and 1 year after the treatment 17( 14.3%) patients were dead. There were higher rate of disturbance of Consciousness、irratation and epilepsy present in these 17 patients as they come to our hospital. The majority patients(64.7%)of these 17 patients were evaluated as severity(MRC 3) TBM once they were admitted, while there were still na few patients were only deemed as light symptoms(MRC 1). 2.There was higher rate of patients with increased intracranial pressure(>180mm H2O) and great increased intracranial pressure(>330mm H2O) in the dead group,but there was no difference of CSF WBC counts、protein、Ig G、Ig M. 3.The patients who died within on year after enrollment were all used to be treated by glucocorticoid. 3. 96 TBM patients with Informed consent were detected the gene polymorphisms of LTA4 H rs17525495: 66 CC type,21 C T type and 9 TT type。The T allele frequency T is about 20.5%. 4. In the TT Group, there were more patients were evaluated as MRC1(p<0.05)but have more patients have fever and Nuchal rigidity(p<0.05)。There was higher rate of patients with increased Ig M,but there was no difference of CSF WBC counts、protein、Ig G、Ig A(p<0.05).5. The patients who died within 1 year in TT and CT group has already been evaluated as moderate(MRC2) and serious symptom( MRC3), while the patients who died within 1 year in CC group has only been evaluated as light symptom( MRC1). 6.Patients with TBM had higher CSF LTB4 levels than patients with CM、CNSL and NIND. A positive correlation was observed between the CSF LTB4 levels and Neutrophil number and Neutrophil/WBC(White blood cell) ration but not between the CSF LTB4 levels and Neutrophil number and WBC number in the CSF. There is no significant difference of CSF LTB4 levels between the different severity groups.Conclusion:The majority of patients with bad outcome were valued as moderate or serious symptom(MRC2 and 3), there were still a few patients who were admitted only with light symptom(MRC1) and had progressive disease course even with the anti-TB therapies. The detection of SNP of LTA4 H rs17525495 revealed that these patients who died within 1 year after therapy with MRC1 were all CC type, it indicated that the poor response of patients to anti-TB and steroid treatment may not all be due to increased inflammation in the CSF. The increase of CSF LTB4 concentration in TBM patients may reflect the inflammation levels of CSF but whether it can be an indicator of steroid response should be further explored.