Correlation between inflammatory mediators and biochemical markers in patients with active pulmonary tuberculosis

Authors

DOI:

https://doi.org/10.11606/issn.2176-7262.rmrp.2023.208110

Keywords:

Biochemistry, Cytokines , Inflammation mediators, Pulmonary tuberculosis

Abstract

Objective: Correlate inflammatory mediators and biochemical parameters in patients with active pulmonary tuberculosis (TB) treated at a public hospital in São Luís, MA. Methods: This is a case-control study of patients with a positive
diagnosis of active pulmonary TB. Serum samples from patients and the control group were collected for the clinical trials, and epidemiological data were collected through medical records and interviews. The control group consisted of healthy volunteers with no previous contact with TB cases, matched by age and sex to the clinical group. To measure
inflammatory cytokines, we used the Human IL-6 ELISA Set and Human IFN-γ ELISA Set kits. Oxidative stress was measured by quantification of thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO). In biochemistry, the levels of uric acid, anti-streptolysin “O” (AEO), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), calcium, total cholesterol, gamma-glutamyl transferase (Gamma GT), glucose, alkaline phosphatase, high-density lipoprotein (HDL), C-reactive protein (CRP) and triglycerides were measured. Results: The clinical group consisted of 53 patients. There was a substantial decrease in IFN-γ (p<0.0001) and a significant increase in IL-6 (p<0.0001). TBARS production increased significantly (p= 0.0414). There was no significant difference in NO production (p= 0.3194). In biochemistry, there was a significant increase in ALT (p= 0.0072), AST (p= 0.0016), Gamma GT (p= 0.0011), alkaline phosphatase (p<0.0001), CRP (p<0. .0001) and triglycerides (p= 0.0343), and a significant decrease in calcium (p<0.0001). A significant positive correlation was found between IL-6 and IFN-γ (p= 0.0448), as well as AST and ALT (p<0.0001); CRP and gamma GT (p<0.0001); Gamma GT and ALT (p= 0.0016); Gamma GT and AST (p=0.0004); triglycerides and cholesterol (p= 0.0002); alkaline phosphatase and gamma GT (p<0.0001); CRP and alkaline phosphatase (p<0.0001); triglycerides and calcium (p= 0.0121); cholesterol and calcium (p= 0.0261); glucose and cholesterol (p= 0.0373); and triglycerides and glucose (p= 0.0127) in biochemistry, with a significant negative correlation between glucose and uric acid (p= 0.0092); and CRP and HDL (p=0.0037). The correlation between inflammatory mediators and biochemical markers was positive between IL-6 and gamma GT (p= 0.0011); IL-6 and CRP (p<0.0001); IL-6 and alkaline phosphatase (p=0.0076); and NO and triglycerides (p= 0.0016), and significant negative correlation between IFN-γ and cholesterol (p= 0.0171) and TBARS and cholesterol (p= 0.0138). Conclusion: Immunosuppression of IFN-γ activity was observed. A correlation was found between IL-6 and inflammatory biochemical markers, indicating damage and injury caused by M. tuberculosis.

Downloads

Download data is not yet available.

Author Biographies

  • Danyelle Cristina Pereira Santos, Universidade Ceuma. Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil.

    Pós-graduanda em Biologia Microbiana

  • Amanda Caroline de Souza Sales, Universidade Ceuma. Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil.

    Pós-graduanda em Biologia Microbiana

  • Douglas Henrique dos Santos Silva, Universidade Ceuma. Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil.

    Pós-graduanda em Biologia Microbiana

  • Érika Alves da Fonseca Amorim, Universidade Ceuma. Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil.

    Pós-graduanda em Odontologia

  • Silvana Jozie Assunção Braga Bacelar Lobato, Universidade Ceuma. Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil.

    Pós-graduanda em Programas e Serviços de Saúde

  • Eduardo Martins de Sousa, Universidade Ceuma. Laboratório Virologia, São Luís, (MA), Brasil.

    Pós-graduando em Biologia Microbiana

  • Luís Cláudio Nascimento da Silva, Universidade Ceuma.Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil

    Pós-graduando em Biologia Microbiana

  • Adrielle Zagmignan, Universidade Ceuma.Laboratório de Patogenicidade Microbiana, São Luís, (MA), Brasil.

    Pós-graduanda em Biologia Microbiana

References

Houben RMGJ, Dodd, PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med. 2016;13(10):e1002152. DOI: https://doi.org/10.1371/journal.pmed.1002152.

World Health Organization (WHO). Tuberculosis [internet]. 2023. Disponível em: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022.

Ministério da Saúde (Brasil). Sistema de Informação de Agravos de Notificação - Sinan Net. Tuberculose - casos confirmados notificados no sistema de informação de agravos de notificação – Maranhão. Brasília: Ministério da Saúde; 2023.

Koch A, Mizrahi V. Mycobacterium tuberculosis. Trends Microbiol. 2018;26(6):555–6. DOI: https://doi.org/10.1016/j.tim.2018.02.012.

Miggiano R, Rizzi M, Ferraris DM. Mycobacterium tuberculosis Pathogenesis, Infection Prevention and Treatment. Pathogens. 2020;9(5):385. DOI: https://doi.org/10.3390/pathogens9050385.

Dannenberg Jr AM. Immune mechanisms in the pathogenesis of pulmonary tuberculosis. Rev Infect Dis. 1989;11(Suppl 2):S369-78. DOI: https://doi.org/10.1093/clinids/11.supplement_2.s369.

Abbas AK, Lichtman AH, Pillai S. Imunologia Celular e Molecular. 9a. ed. Rio de Janeiro: Elsevier; 2019.

Domingo-Gonzalez R, Prince O, Cooper A, Khader AS. Cytokines and chemokines in Mycobacterium tuberculosis infection. Microbiol Spectr. 2016;4(5): 10.1128/microbiolspec.TBTB2-0018-2016. DOI: https://doi.org/10.1128/microbiolspec.tbtb2-0018-2016.

Palucci I, Delogu G. Host directed therapies for tuberculosis: futures strategies for an ancient disease. Chemotherapy. 2018;63(3):172-180. DOI: https://doi.org/10.1159/000490478.

Chaves LB, Souza TF, Silva MVC, Oliveira CF, Lipp MEN, Pinto ML. Estresse em universitários: análise sanguínea e qualidade de vida. Rev Bras Ter Cogn. 2016;12(1):20-6. DOI: http://dx.doi.org/10.5935/1808-5687.20160004.

Buege JA, AUST SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10. DOI: https://doi.org/10.1016/s0076-6879(78)52032-6.

Griess P. Bemerkungen zu der abhandlung der H.H. Weselsky und Benedikt “Ueber einige azoverbindungen”. Ber Dtsch Chem Ges. 1879;12(1):426-8. DOI: https://doi.org/10.1002/cber.187901201117.

Wang Y, Xie J, Wang N, Li Y, Sun X, Zhang Y, et al. Lactobacillus casei Zhang modulate cytokine and toll-like receptor expression and beneficially regulate poly I:C-induced immune responses in RAW264.7 macrophages. Microbiol Immunol. 2013;57(1):54-62. DOI: https://doi.org/10.1111/j.1348-0421.516.x

Baba RK, Vaz MSMG, da Costa J. Correlação de dados agrometeorológicos utilizando métodos estatísticos. Rev Bras Meteorol. 2014;29(4):515-26. DOI: https://doi.org/10.1590/0102-778620130611.

Van Acker H, Coenye T. The Role of Reactive Oxygen Species in Antibiotic-Mediated Killing of Bacteria. Trends Microbiol. 2017;25(6):456-66. DOI: https://doi.org/10.1016/j.tim.2016.12.008.

Shastri MD, Shukla SD, Chong WC, Dua K, Peterson GM, Patel RP, et al. Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis. Oxid Med Cell Longev. 2018;2018:7695364. DOI: https://doi.org/10.1155/2018/7695364.

Bolajoko EB, Arinola OG, Odaibo GN, Maiga M. Plasma levels of tumor necrosis factor-alpha, interferon-gamma, inducible nitric oxide synthase, and 3-nitrotyrosine in drug-resistant and drug-sensitive pulmonary tuberculosis patients, Ibadan, Nigeria. Int J Mycobacteriol. 2020;9(2):185-9. DOI: https://doi.org/10.4103/ijmy.ijmy_63_20.

Han F, Li S, Yang Y, Bai Z. Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid peroxidation and disrupting iron homeostasis. Bioengineered. 2021;12(1):5279-88. DOI: https://doi.org/10.1080/21655979.2021.1964158.

Ledesma JR, Ma J, Zheng P, Ross JM, Vos T, Kyu HH. Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis. BMC Infect Dis. 2021;21(1):467. DOI: https://doi.org/10.1186/s12879-021-06141-4.

Casanova JL, Abel L. Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol. 2002;20:581-620. DOI: https://doi.org/10.1146/annurev.immunol.20.081501.125851.

Sologuren I, Boisson-Dupuis S, Pestano J, Vincent QB, Fernández-Pérez L, Chapgier A, et al. Partial recessive IFN-γR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds. Hum Mol Genet. 2011;20(8):1509-23. DOI: https://doi.org/10.1093/hmg/ddr029.

Ramirez-Alejo N, Santos-Argumedo L. Innate defects of the IL-12/IFN-γ axis in susceptibility to infections by mycobacteria and salmonella. J Interferon Cytokine Res. 2014;34(5):307-17. DOI: https://doi.org/10.1089/jir.2013.0050.

Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinica features of inborn errors of IFN-γ immunity. Semin Immunol. 2014;26(6):454-70. DOI: https://doi.org/10.1016/j.smim.2014.09.008.

Nagabhushanam V, Solache A, Ting LM, Escaron CJ, Zhang JY, Ernst JD. Innate inhibition of adaptive immunity: Mycobacterium tuberculosis-induced IL-6 inhibits macrophage responses to IFN-gamma. J Immunol. 2003;171(9):4750-7. DOI: https://doi.org/10.4049/jimmunol.171.9.4750.

Dutta RK, Kathania M, Raje M, Majumdar S. IL-6 inhibits IFN-γ induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages. Int J Biochem Cell Biol. 2012;44(6):942-54. DOI: https://doi.org/10.1016/j.biocel.2012.02.021.

Rath S, Narasimhan R, Lumsden C. C-reactive protein (CRP) responses in neonates with hypoxic ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2014;99(2):F172. DOI: https://doi.org/10.1136/archdischild-2013-304367.

Rajopadhye SH, Mukherjee SR, Chowdhary AS, Dandekar SP. Oxidative Stress Markers in Tuberculosis and HIV/TB Co-Infection. J Clin Diagn Res. 2017;11(8):BC24-BC28. DOI: https://doi.org/10.7860/jcdr/2017/28478.10473.

Soares AMSS. Tuberculose no Centro Hospitalar Cova da Beira e a sua relação com a imunodepressão. [dissertação]. Covilhão: Universidade da Beira Interior; 2014. 43 f.

Pinho L, Oliveira S, Serino J, Febra T, Ramos S, Silva C, et al. Tuberculose miliar no século XXI–a propósito de um caso clínico. Nascer Crescer. 2014;21(2):151-4.

Enoh JE, Cho FN, Manfo FP, Ako SE, Akum EA. Abnormal Levels of Liver Enzymes and Hepatotoxicity in HIV-Positive, TB, and HIV/TB-Coinfected Patients on Treatment in Fako Division, Southwest Region of Cameroon. Biomed Res Int. 2020;2020:9631731. DOI: https://doi.org/10.1155/2020/9631731.

Su Q, Liu Q, Liu J, Fu L, Liu T, Liang J, et al. Study on the associations between liver damage and antituberculosis drug rifampicin and relative metabolic enzyme gene polymorphisms. Bioengineered. 2021;12(2):11700-8. DOI: https://doi.org/10.1080/21655979.2021.2003930.

Brown J, Clark K, Smith C, Hopwood J, Lynard O, Toolan M, et al. Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis. BMC Infect Dis. 2016;16:265. DOI: https://doi.org/10.1186/s12879-016-1612-1.

Ufoaroh CU, Onwurah CA, Mbanuzuru VA, Mmaju CI, Chukwurah SN, Umenzekwe CC, et al. Biochemical changes in tuberculosis. Pan Afr Med J. 2021;38:66. DOI: https://doi.org/10.11604/pamj.2021.38.66.21707.

Nordestgaard BG, Langsted A, Mora S, Kolovou G, Baum H, Bruckert E, et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J. 2016;37(25):1944-58. DOI: https://doi.org/10.1093/eurheartj/ehw152.

Metwally MM, Raheem H. Lipid profile in tuberculous patients: a preliminar report. Life Sci. 2012;9(1):719-22.

Gebremicael G, Amare Y, Challa F, Gebreegziabxier A, Medhin G, Wolde M, et al. Lipid Profile in Tuberculosis Patients with and without Human Immunodeficiency Virus Infection. Int J Chronic Dis. 2017;2017:3843291. DOI: https://doi.org/10.1155/2017/3843291.

Chidambaram V, Zhou L, Ruelas Castillo J, Kumar A, Ayeh SK, Gupte A, et al. Higher Serum Cholesterol Levels Are Associated With Reduced Systemic Inflammation and Mortality During Tuberculosis Treatment Independent of Body Mass Index. Front Cardiovasc Med. 2021;8:696517. DOI: https://doi.org/10.3389/fcvm.2021.696517.

Hall JE, Hall ME. Guyton & Hall – Tratado de Fisiologia Médica. 14a. ed. Barueri: Editora Gen – Grupo Editorial Nacional Part S/A. 2021.

Hafiez AA, Abdel-Hafez MA, Salem D, Abdou MA, Helaly AA, Aarag AH. Calcium homeostasis in untreated pulmonary tuberculosis. I--Basic study. Kekkaku. 1990;65(5):309-16.

Mehto S, Antony C, Khan N, Arya R, Selvakumar A, Tiwari BK, et al. Mycobacterium tuberculosis and Human Immunodeficiency Virus Type 1 Cooperatively Modulate Macrophage Apoptosis via Toll Like Receptor 2 and Calcium Homeostasis. PLoS One. 2015;10(7):e0131767. DOI: https://doi.org/10.1371/journal.pone.0131767.

Published

2023-11-27

Issue

Section

Original Articles

How to Cite

1.
Santos DCP, Sales AC de S, Silva DH dos S, Amorim Érika A da F, Lobato SJABB, Sousa EM de, et al. Correlation between inflammatory mediators and biochemical markers in patients with active pulmonary tuberculosis. Medicina (Ribeirão Preto) [Internet]. 2023 Nov. 27 [cited 2024 Jun. 26];56(3):e-208110. Available from: https://journals.usp.br/rmrp/article/view/208110