Features of cytokine production in patients with pulmonary tuberculosis during specific chemotherapy

I n t r o d u c t i o n . Currently, immunological research is one of the priorities in the field of tuberculosis, since the effectiveness of treatment and, consequently, the outcome of the disease in most cases are determined by the immune and genetic characteristics of the macroorganism.

A i m . To study the dynamics of cytokines (IL-6, IL-8, IL-4, IL-10, TNF-α, IFN-γ) in patients with  pulmonary disseminated tuberculosis (DST) and fi brous-cavernous tuberculosis (FCT)  after 2 months of specific chemotherapy.

M a t e r i a l s a n d m e t h o d s . The study group consisted of 100 patients with pulmonary tuberculosis (DST – 48 people, FCT – 52 people) aged 40 to 69 years who received specific chemotherapy in the intensive phase.  The concentration of  cytokines (IL-6, IL-8, IL-4, IL-10, TNF-α, IFN-γ) was determined at baseline and after 2 months of chemotherapy, as well as  the cytokine balance (IL-6 + IL-8/IL-4 + IL-10) at baseline and after 2 weeks of chemotherapy. R e s u l t s . After 2 months of chemotherapy, patients with DST showed a signifi cant decrease in the level of IFN-γ, TNF-α, IL-6, IL-10, and the level of IL-8 tended to increase, however, this dynamic was not statistically significant; in patients with FCT, there was a significant decrease in the level of IFN-γ, IL-8, IL-6, as well as IL-4 – from 5.6 to 5.11 pg/ml, TNF-α – from 3.6 to 3.1 pg/ml, however, this trend was not statistically significant. The cytokine balance values tended to decrease: in patients with DST – from 7.7 to 7.48, and in patients with FCT – from 7.69 to 4.97.

C o n c l u s i o n . The cytokine system plays an important role in the regulation of infl ammatory processes in patients with DST and FCT of lungs.

1. Global Tuberculosis Report/World Health Organization. 2022. URL: https://www.who.int/publications/i/item/9789240061729.

2. Bo H., Moure U., Yang Y. et al. Mycobacterium tuberculosis – macrophage interaction. Front. Cell. Infect. Microbiol. 2023;13:1-14. DOI: 10.3389/fcimb.2023.1062963.

3. Ndong Sima C.A.A., Smith D., Petersen D. et al. The immunogenetics of tuberculosis (TB) susceptibility. Immunogenetics. 2023;75(3):215-230. DOI: 10.1007/s00251 022-91-01-290-5.

4. da Silva Graça Amoras E., Morais T., do Nascimento Ferreira R. et al. Association of cytokine gene polymorphism and their impact on active and latent tuberculosis in Brazil’s Amazon Region. Biomolecules. 2023;13(10):1541. DOI: 10.3390/biom13101541.

5. Natarajan S., Ranganathan M., Hanna L.E., Tripathy S. Transcriptional profi ling and deriving a seven-gene signature that discriminates active and latent tuberculosis: An integrative bioinformatics approach. Genes (Basel). 2022;3(4):616. DOI: 10.3390/genes13040616.

6. Suzukawa M., Takeda K., Akashi S. et al. Evaluation of cytokine levels using QuantiFERON-TB Gold Plus in patients with active tuberculosis. J. Infect. 2020;80(5):547-553. DOI: 10.1016/j.jinf.2020.02.007.

7. Bade P., Simonetti F., Sans S. et al. Integrative analysis of human macrophage infl ammatory response related to Mycobacterium tuberculosis virulence. Front. Immunol. 2021;(12):668060. DOI: 10.3389/fimmu.2021.668060.

8. Boni F.G., Hamdi I., Koundi L.M. et al. Cytokine storm in tuberculosis and IL-6 involvement. Infect. Genet. Evol. 2022;97:105166. DOI: 10.1016/j.meegid.2021.105166.

9. Goretskaya M.V. (2017). Features of the immune system in infection with Mycobacterium tuberculosis. In Actual Questions of Microbiology, Immunology and Infectology: Collection of writings of scientific and practical conference. Grodno. 24–27 p. (In Russ.)

10. Saghazadeh A., Rezaei N. Central infl ammatory cytokines in tuberculous meningitis: A systematic review and metaanalysis. J. Interferon Cytokine Res. 2022;42(3):95-107. DOI. 10.1089/2021.0176.

11. Barnacle J.R., Davis A.G., Wilkinson R.J. Recent advances in understanding the human host immune response in tuberculous meningitis. Front. Immunol. 2024;14:1326651. DOI: 10.3389/fimmu.2023.1326651.

12. Zhivechkova E.A., Lapshtaeva A.V. The role of cytokines in the initiation and course of lung tuberculosis: a modern view. Astrakhan medical journal. 2019;14(4):17-28. DOI: 10.17021/2019.14.4.17.28. (In Russ.)

13. Mezentseva M.V., Stakhanov V.A., Zakharova M.V. et al. Cytokines as markers of the infi ltrative pulmonary tuberculosis development. Infection and Immunity. 2011. 1(4):367-362. (In Russ.)

14. Marino S., Myers A., Flynn J., Kirschner D. TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: A next-generation two-compartmental model. J. Theor. Biol. 2010;265(4):586-598. DOI: 10.1016/j.jtbi.2010.05.012.

15. Churina E.G., Urazova O.I., Novitsky V.V. et al. Functional polymorphism of the pro-inflammatory cytokine genes in pulmonary tuberculosis. Medical Immunology (Russia). 2019;21(1):149-156. DOI: 10.15789/15630625-2019-1-149-156. (In Russ.)

16. Churina E.G., Urazova O.I., Sitnikova A.V. et al. Differentiation of blood monocytes and features of the cytokine status in patients with lung tuberculosis. Pathological physiology and experimental therapy. 2020;64(4):79-87. DOI: 0.25557/00312991.2020.04.79-87. (In Russ.)

17. Alymenko M.A., Valiev R.Sh., Valiev N.R. et al. Associations between the gene polymorphism of cytokines and the level of their production in patients with pulmonary tuberculosis. Siberian Medical Review. 2024;2(146):56-63. DOI: 10.20333/25000136-20242-56-63. (In Russ.)

18. Kitaev M.I., Dudenko E.V., Sydykova S.S. et al. Production dynamics of cytokines in patients with extrapulmonary tuberculosis under treatment. Herald of the Kyrgyz-Russian Slavic University. 2014;14(4):98-100. (In Russ.)