Dynamics of cytokine profile indexes in children with first diagnosed pulmonary tuberculosis in the course of antimycobacterial therapy
DOI:
https://doi.org/10.14739/2310-1210.2018.02.125171Keywords:
cytokines, children, tuberculosis, treatmentAbstract
Antimycobacterial therapy is the main method of tuberculosis treatment. But some antimycobacterial medications have an unfavorable influence on the immune system and this fact significantly decreases efficiency of treatment and requires an additional pathogenetic immunocorrection.
The aim of the work – to research dynamics of cytokine profile indexes in blood serum of children with first diagnosed pulmonary tuberculosis in the course of antimycobacterial therapy depending on specific process prevalence and to assess efficiency of antimycobacterial therapy after the basic course of treatment completion for further immunocorrecting therapy development.
Materials and methods. Study of cytokine profile indexes was performed in 28 children with first diagnosed pulmonary tuberculosis from 1 to 16 years old (the average age was 9.2 ± 1.1 years). Depending on the specific process prevalence children with first diagnosed pulmonary tuberculosis were divided into two groups: the first group included 17 persons with a disseminated process and the second group included 11 persons with an isolated process. The comparison group included 30 healthy children. Comparison groups were age-matched and gender-matched. Cytokine profile indexes were studied by means of IL-2, IL-6, IL-4, IL-10 levels detection in blood serum through enzyme-linked immunosorbent assay using immunoenzymometric reader Sirio S and a set “Bender MedSystems GmbH” (Austria), (pg/ml). Dynamics of cytokine indexes was studied at the beginning of the antimycobacterial therapy intensive phase, on completion of the antimycobacterial therapy intensive phase (2 months after treatment) and on completion of the antimycobacterial therapy maintenance phase (6 months after treatment). Parents of all sick children signed patient’s written informed consent for participation in this study. Results of this work were processed by the modern methods of analysis with the help of a personal computer and the statistical package of the licensed software program Statistica® for Windows 6.0 (StatSoft Inc., № AXXR712 D833214FAN5).
Results. A significantly high level of pro-inflammatory cytokine IL-2 characterized Тh1-type of cellular immune response high activity in children with first diagnosed pulmonary disseminated tuberculosisthroughout the entire course of antimycobacterial therapy. And significantly stably low levels of anti-inflammatory cytokines IL-4 and IL-10 indicated insufficiency of anti-inflammatory response throughout the entire course of antimycobacterial therapy. Calculation of cytokine indexes (and namely the IL-2/IL-10 ratio) has conformed that there was a disbalance between pro-inflammatory and anti-inflammatory cytokines towards pro-inflammatory cytokines with predominance of Тh1-type cellular immune response which lasted during the entire course of antimycobacterial therapy and tended to decline on its completion. Even though that in the course of antimycobacterial therapy in children with bacterioexcretion this process stopped, average duration of in-patient treatment was 9–10 months and that was 3 months longer than standard treatment of patients with first diagnosed pulmonary tuberculosis. The warning sign is also that among children with disseminated tuberculosis there were 3 cases (17.6 %) of multidrug-resistant tuberculosis in the course of treatment and in case with 1 child (5.9 %) lung destruction was persisted on the treatment completion.
Conclusions. Children with first diagnosed pulmonary tuberculosis (regardless of the specific process prevalence) had a high activity of Th1-type cellular immune response against the background of an extremely decreased activity of Th2-type cellular immune response throughout the entire course of antimycobacterial therapy. This fact indicates insufficiency of anti-inflammatory response. At the same time all children had a pronounced disbalance between pro-inflammatory and anti-inflammatory cytokines towards pro-inflammatory ones on completion of the treatment basic course. These changes may contribute to the specific process progression as well as early recurrences of the disease.
References
Belogortseva, O. I. (2014). Epidemiolohichna sytuatsiia shchodo tuberkulozu u ditei v Ukraini ta shliakhy udoskonalennia nadannia protytuberkuloznoi dopomohy ditiam [The epidemiological situation of tuberculosis in children in Ukraine and ways to improve TB care to children]. Sovremennaya pediatriya, 5, 22–26. [in Ukrainian].
Bilogortseva, O. I., Pobedonna, G. P., Rekalova, O. M., Dotsenko, Ya. I., Koposova, I. V., & Firsova, A. P. (2015). Osoblyvosti stanu imunitetu u ditei, khvorykh na vpershe diahnostovanyi tuberkuloz [Peculiarities of immune stаtus in children with newly diagnosed tuberculosis]. Ukrainskyi pulmonolohichnyi zhurnal, 3, 20–24. [in Ukrainian].
Shalmin, O. S., Raznatovska, O. M., Abramov, A. V., & Zhernova, H. O. (2011). Osoblyvosti tsytokinovoho profiliu u khvorykh na khimiorezystentnyi tuberkuloz lehen [Specificity of the cytokine profil in hvorih on chemorioresistent tuberculosis]. Ukrainskyj zhurnal klininichnoi ta laboratrnoi medytsyny, 2, 68–71. [in Ukrainian].
Mezentseva, M. V., Stakhanov, V. A., Zakharova, M. V., Zotova, I. F., Tregubova, M. I., & Shapoval, I. M. (2011). Citokiny kak markery razvitiya infil'trativnogo tuberkuleza legkikh [Cytokines as markers of the infiltrative pulmonary tuberculosis development]. Infekciya i immunitet, 1(4), 367–372. [in Russian].
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 hvoroby, VIL-infektsiia, 1(28), 42–47. [in Ukrainian].
Vivchar, I. S., & Zaleckij, N. P. (2013). Korrelyacionnye svyazi pokazatelej immunnogo i citokinovogo statusa u detej i podrostkov, bol'nykh tuberkulezom legkikh. [Correlation of indicators immune and cytokine status in children and adolescents with pulmonary tuberculosis]. Sovremennye problemy nauki i obrazovaniya, 6. [in Russian].
Martinez, A. N., Mehra, S., & Kaushal, D. (2013). Role of interleukin 6 in innate immunity to Mycobacterium tuberculosis infection. J Infect Dis, 207(8), 1253–61. doi: 10.1093/infdis/jit037.
Redford, P. S., Murray, P. J., & Garra, A. O. (2011). The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunology, 4(3), 261–270. doi:10.1038/mi.2011.7.
Peresi, E., Silva, S. M., Calvi, S. A., & Marcondes-Machado, J. (2008). Cytokines and acute phase serum proteins as markers of inflammatory regression during the treatment of pulmonary tuberculosis. Jornal Brasileiro de Pneumologia, 34(11), 942–949.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
