The effect of immunomodulator azoximer bromide on the cytokine profile in a complex therapy for children with newly diagnosed tuberculosis
DOI:
https://doi.org/10.14739/2310-1210.2022.2.249347Keywords:
tuberculosis, children, immunomodulator, cytokinesAbstract
Aim. To analyze the effect of immunomodulator azoximer bromide on the serum cytokine profile (IL-2, IL-6, IL-4, IL-10) in the complex therapy for children with newly diagnosed tuberculosis (TB).
Materials and methods. The study included 51 newly diagnosed TB children, who were divided into 2 groups: 26 children received immunomodulator azoximer bromide (main group) in combined therapy with concurrent antimycobacterial therapy (AMBT) and 25 children were assigned to only AMBT (control group). The main group children received azoximer bromide (immunomodulator) adjunctive therapy for immunological changes correction concurrently with the standard AMBT: children under the age of 10 years – orally 6 mg twice a day, children aged over 10 years – 12 mg twice a day; the treatment course – 14 days. The serum cytokine profile (IL-2, IL-6, IL-4, IL-10) was examined on the basis of the Immunological Department in the Training Medical and Laboratory Center of ZSMU by solid-phase enzyme-linked immunosorbent assay (ELISA) using a device ELISA – reader Sirio S with respective kits (Bender MedSystems GmbH, Austria, pcg/ml) before AMBT initiation and at the end of AMBT maintenance phase (MF). The study results were processed on a personal computer using the statistical package of the licensed program Statistica, version 13 (Copyright 1984–2018 TIBCO Software Inc. All rights reserved, License No. JPZ8041382130ARCN10-J).
Results. At the AMBT initiation, newly diagnosed TB children of both groups showed a clear imbalance between pro- and anti-inflammatory cytokines towards pro-inflammatory ones with a predominance and high activity of Th1 type cellular immune response. The ratios of IL-2/IL-10 and IL-6/IL-10 pointed to the normalized balance in the regulatory system of pro- and anti-inflammatory cytokines in the main group children upon the MF of AMBT completion. The ratio of IL-2/IL-10 dropped 7.3-fold at the treatment completion relative to that at the initiation of treatment, however, compared to the control group at the end of treatment, it was 7.2 times less. The controls did not show significant on-treatment dynamics of the IL-2/IL-10 and IL-6/IL-10 ratios, the IL-2/IL-10 ratio was 12.8 times higher than in the healthy children group at the treatment completion.
Conclusions. The use of immunomodulator azoximer bromide in combination therapy for newly diagnosed TB children helps to normalize all cytokine profiles and the balance in the regulatory system of pro- and anti-inflammatory cytokines after the AMBT completion. Therefore, the effect of immunomodulator azoximer bromide on the cytokine profile in the treatment for newly diagnosed TB children is substantial, which would increase the AMBT effectiveness among this patient group as a whole.
References
Public Health Center of the Ministry of Health of Ukraine. (2021). Statystyka z tuberkulozu [Tuberculosis statistics]. https://www.phc.org.ua/kontrol-zakhvoryuvan/tuberkuloz/statistika-z-tb [in Ukrainian].
Jenkins, H. E., Yuen, C. M., Rodriguez, C. A., Nathavitharana, R. R., McLaughlin, M. M., Donald, P., Marais, B. J., & Becerra, M. C. (2017). Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis. The Lancet. Infectious Diseases, 17(3), 285-295. https://doi.org/10.1016/S1473-3099(16)30474-1
Dodd, P. J., Yuen, C. M., Sismanidis, C., Seddon, J. A., & Jenkins, H. E. (2017). The global burden of tuberculosis mortality in children: a mathematical modelling study. The Lancet. Global Health, 5(9), e898-e906. https://doi.org/10.1016/S2214-109X(17)30289-9
Druszczynska, M., Seweryn, M., Wawrocki, S., Kowalewska-Pietrzak, M., Pankowska, A., & Rudnicka, W. (2021). Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children. Pathogens, 10(5), Article 517. https://doi.org/10.3390/pathogens10050517
Piskur, Z. I., Mykolyshyn, L. I., Platonova, I. L., & Lapovets, L. Ye. (2017). Osoblyvosti tsytokinovoho spektra IL-1β, IL-2, IL-10 i TNF-α u ditei, khvorykh na tuberkuloz [Peculiarities of cytokine spectrum IL‑1β, IL‑2, IL‑10 and TNF-α in children with tuberculosis]. Tuberkuloz, lehenevi khvoroby, VIL-infektsiia, (1), 42-47. [in Ukrainian].
Hemingway, C., Berk, M., Anderson, S. T., Wright, V. J., Hamilton, S., Eleftherohorinou, H., Kaforou, M., Goldgof, G. M., Hickman, K., Kampmann, B., Schoeman, J., Eley, B., Beatty, D., Pienaar, S., Nicol, M. P., Griffiths, M. J., Waddell, S. J., Newton, S. M., Coin, L. J., Relman, D. A., … Levin, M. (2017). Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function. PLOS ONE, 12(11), Article e0185973. https://doi.org/10.1371/journal.pone.0185973
Pritulina, Yu. G., Krivoruchko, I. V., Shentsova, V. V., Fil, G. V., Astapchenko, D. S., & Sakharova, L. A. (2014). Prakticheskaya znachimost' analiza tsitokinovogo profilya pri ryade infektsionnykh zabolevanii [The practical significance of cytokine profile analysis of in a number of infectious diseases]. Aktualna infektolohiia, (1), 40-44. [in Russian].
Gutiérrez-González, L. H., Juárez, E., Carranza, C., Carreto-Binaghi, L. E., Alejandre, A., Cabello-Gutiérrrez, C., & Gonzalez, Y. (2021). Immunological Aspects of Diagnosis and Management of Childhood Tuberculosis. Infection and Drug Resistance, 14, 929-946. https://doi.org/10.2147/IDR.S295798
Le Boedec, K. (2016). Sensitivity and specificity of normality tests and consequences on reference interval accuracy at small sample size: a computer-simulation study. Veterinary Clinical Pathology, 45(4), 648-656. https://doi.org/10.1111/vcp.12390
Vetter, T. R. (2017). Descriptive Statistics: Reporting the Answers to the 5 Basic Questions of Who, What, Why, When, Where, and a Sixth, So What? Anesthesia & Analgesia, 125(5), 1797-1802. https://doi.org/10.1213/ANE.0000000000002471
Bishara, A. J., & Hittner, J. B. (2012). Testing the significance of a correlation with nonnormal data: Comparison of Pearson, Spearman, transformation, and resampling approaches. Psychological Methods, 17(3), 399-417. https://doi.org/10.1037/a0028087
Bakker, M., & Wicherts, J. M. (2014). Outlier removal, sum scores, and the inflation of the type I error rate in independent samples t tests: The power of alternatives and recommendations. Psychological Methods, 19(3), 409-427. https://doi.org/10.1037/met0000014
Kuzhko, M. M., Butov, D. O., Stepanenko, H. L., Hrynishyna, O. O., & Maksymenko, O. A. (2012). Vplyv tsytokiniv na moduliatsiiu monoklonalnykh antytil krovi u khvorykh iz vpershe diahnostovanym tuberkulozom lehen [Effect of cytokines on the modulation of the blood monoclonal antibodies in patients with new-onset pulmonary tuberculosis]. Tuberkuloz, lehenevi khvoroby, VIL-infektsiia, (3), 29-32. [in Ukrainian].
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