Nitric oxide in cerebrospinal fluid of central nervous system tuberculosis: correlations with culture, antibody response, and cell count
Nitric oxide in cerebrospinal fluid of central nervous system tuberculosis: correlations with culture, antibody response, and cell count
Background/aim: The role of nitric oxide (NO) has been established in infection over the years. NO functions by inhibiting the growth of intracellular pathogens. The present study was undertaken to ascertain the role of NO in central nervous system (CNS) infection by Mycobacterium tuberculosis. Materials and methods: A total of 781 chronic meningitis cerebrospinal fluid (CSF) samples suspected of CNS tuberculosis (TB) were categorized based on M. tuberculosis culture positivity, anti-TB antibody response, and CSF cell count and were analyzed for NO. Results: We found that NO levels were positive in 10.88% of the CSF samples. Positivity for NO was 18%, 11.67%, 13.68%, 9.32%, and 9.66% in the cases with mycobacterial culture positivity, anti-TB antibody positivity, high cell count, low cell count, and zero cell count, respectively. Among the above cell count categories, NO levels were noticed to be elevated in high cell count samples with mononuclear cell predominance. Conclusion: This study suggests that NO might play some role in the later stages of tuberculous meningitis. This is the first study to our knowledge in which NO was evaluated in CSF in relation to immune response and the presence of a pathogen with such a large number of subjects.
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- 1. Grandgirard D, Gäumann R, Coulibaly B, Dangy JP, Sie A, Junghanss T, Schudel H, Pluschke G, Leib SL. The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis. Mediators Inflamm 2013; 2013: 312476.
- 2. Yang CS, Yuk JM, Jo EK. The role of nitric oxide in mycobacterial infections. Immune Netw 2009; 9: 46-52.
- 3. Denis M. Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cell Immunol 1991; 132: 150-157.
- 4. Kwon OJ. The role of nitric oxide in the immune response of tuberculosis. J Korean Med Sci 1997; 12: 481-487.
- 5. Burgner D, Rockett K, Kwiatkowski D. Nitric oxide and infectious diseases. Arch Dis Child 1999; 81: 185-188.
- 6. Peterson PK, Hu S, Anderson WR, Chao CC. Nitric oxide production and neurotoxicity mediated by activated microglia from human versus mouse brain. J Infect Dis 1994; 170: 457- 460.
- 7. Bhigjee AI, Padayachee R, Paruk H, Hallwirth-Pillay KD, Marais S, Connoly C. Diagnosis of tuberculous meningitis: clinical and laboratory parameters. Int J Infect Dis 2007; 11: 348-54.
- 8. Thwaites GE, Chau TT, Farrar JJ. Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Microbiol 2004; 42: 378-379.
- 9. Thakur R, Goyal R, Sarma S. Laboratory diagnosis of tuberculous meningitis - is there a scope for further improvement? J Lab Physicians 2010; 2: 21-24.
- 10. Patil SA, Gourie-Devi M, Chaudhuri JR, Chandramuki A. Identification of antibody responses to Mycobacterium tuberculosis antigens in the CSF of tuberculous meningitis patients by Western blotting. Clin Immunol Immunopathol 1996; 81: 35-40.
- 11. Sun J, Zhang X, Broderick M, Fein H. Measurement of nitric oxide production in biological systems by using Griess reaction assay. Sensors 2003; 3: 276-284.
- 12. Tsikas D. Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B 2007; 851: 51-70.
- 13. Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat 2011; 2011: 798764.
- 14. Kapoor N, Narayana Y, Patil SA, Balaji KN. Nitric oxide is involved in Mycobacterium bovis Bacillus Calmette-Guérin activated Jagged1 and Notch1 signaling. J Immunol 2010; 184: 3117-3126.
- 15. Kornelisse RF, Hoekman K, Visser JJ, Hop WC, Huijmans JG, van der Straaten PJ, van der Heijden AJ, Sukhai RN, Neijens HJ, de Groot R. The role of nitric oxide in bacterial meningitis in children. J Infect Dis 1996; 174: 120-126.
- 16. Sáez-Llorens X, Ramilo O, Mustafa MM, Mertsola J, McCracken GH Jr. Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications. J Pediatr 1990; 116: 671-684.
- 17. Çetin K, Erol S, Aksoy H, Taşyaran MA. The relation of cerebrospinal fluid nitric oxide levels to prognosis and differential diagnosis of meningitis. Turk J Med Sci 2002; 32: 385-390.
- 18. Tsukahara H, Haruta T, Hata I, Mayumi M. Nitric oxide in septic and aseptic meningitis in children. Scand J Clin Lab Invest 1998; 58: 73-79.
- 19. Dodd PR, Scott HL, Westphalen RI. Excitotoxic mechanisms in the pathogenesis of dementia. Neurochem Int 1994; 25: 203- 219.
- 20. Olin MR, Armién AG, Cheeran MC, Rock RB, Molitor TW, Peterson PK. Role of nitric oxide in defense of the central nervous system against Mycobacterium tuberculosis. J Infect Dis 2008; 198: 886-889.
- 21. Castillo J, Rama R, Dávalos A. Nitric oxide-related brain damage in acute ischemic stroke. Stroke 2000; 31: 852-857.
- 22. Qureshi GA, Baig SM, Bednar I, Halawa A, Parvez SH. The neurochemical markers in cerebrospinal fluid to differentiate between aseptic and tuberculous meningitis. Neurochem Int 1998; 32: 197-203.
- 23. Fang FC. Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest 1997; 99: 2818-2825.
- 24. Santos PL, Costa RV, Braz JM, Santos LF, Batista AC, Vasconcelos CR, Rangel MR, Ribeiro de Jesus A, de Moura TR, Leopoldo PT et al. Leishmania chagasi naturally resistant to nitric oxide isolated from humans and dogs with visceral leishmaniasis in Brazil. Nitric Oxide 2012; 27: 67-71.
- 25. Duke T, South M, Stewart A. Cerebrospinal fluid nitric oxide metabolites and discrimination of bacterial meningitis from other causes of encephalopathy. Arch Dis Child 1997; 76: 290.