Combined effect of methotrexate and bifidobacteria metabolites on TNFα AND IFNγ production by human peripheral blood mononuclears
- Authors: Ivanova E.V.1, Chaynikova I.N.1, Bekpergenova A.V.1, Bondarenko T.A.1, Chelpachenko O.E.1, Zdvizhkova I.A.1, Perunova N.B.1, Bukharin O.V.1
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Affiliations:
- Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
- Issue: Vol 26, No 3 (2023)
- Pages: 281-286
- Section: SHORT COMMUNICATIONS
- URL: https://ogarev-online.ru/1028-7221/article/view/253403
- DOI: https://doi.org/10.46235/1028-7221-9839-CEO
- ID: 253403
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Abstract
Methotrexate (Mtx) is a first-line drug for the treatment of numerous rheumatic and non-rheumatic disorders, including oncological disdiseases. However, therapeutic efficacy of Mtx is limited by severe toxicity to many organs (myelo-, hepato-, nephrotoxicity, mucositis, enteritis, dysbiosis at various human biotopes, etc.). Recently, a number of studies showed that some metabolites of Bifidobacteria and Lactobacilli are able to enhance effect of chemotherapeutic drugs and limit their toxic properties. The aim of the present work was to study the possible potentiating action of Bifidobacteria cell-free supernatants and methotrexate upon secretion of pro-inflammatory TNFα and IFNγ cytokines by human peripheral blood mononuclear cells (PBMCs). The immunoregulatory effects upon production of TNFα and IFNg was evaluated in the in vitro model of cultured PBMC supplemented with Bifidobacteria metabolites, methotrexate, or their combination. Analysis of the combined effect of Bifidobacteria metabolites and Mtx on the cytokine production revealed their synergism towards the key pro-inflammatory cytokines (TNFα and IFNγ). We found an increase against the control cultures (with Mtx only), inhibition of the early pro-inflammatory cytokine TNFα production. On the contrary, we revealed an increased secretion of IFNγ which regulates the effector cells. The results obtained with these cytokines suggest the presence of a potentiating effect of Bifidobacteria metabolites upon anti-inflammatory and immunoregulatory properties of methotrexate. Thus, Bifidobacteria metabolites can be considered a promising agent which potentiates the therapeutic action of methotrexate by suppressing TNFα secretion and stimulating IFNγ by immunocompetent cells. Further studies of the combined effects of Mtx and metabolites from the intestinal microbiota upon the cytokine production by effector cells could be recommended, aiming to enhance therapeutic effect of methotrexate and limit its toxic properties using the Bifidobacteria metabolites.
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##article.viewOnOriginalSite##About the authors
Elena V. Ivanova
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Author for correspondence.
Email: walerewna13@gmail.com
PhD, MD (Medicine), Associate Professor, Head, Laboratory of Infectious Symbiology
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Irina N. Chaynikova
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: inchainicova@yandex.ru
PhD, MD (Medicine), Professor, Leading Research Associate, Laboratory of Infectious Symbiology
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Anastasia V. Bekpergenova
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: nsavasteeva@gmail.com
ORCID iD: 0000-0001-5020-2493
PhD, Senior Researcher, Laboratory of Infectious Symbiology, Institute of Cellular and Intracellular Symbiosis
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Taisiya A. Bondarenko
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: semenovih88@mail.ru
Research Associate, Laboratory of Infectious symbiology
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Olga E. Chelpachenko
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: oech57@gmail.com
PhD, MD (Medicine), Professor, Leading Research Associate
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Irina A. Zdvizhkova
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: zdvizhkova.irina@gmail.com
Research Associate, Laboratory of Infectious Symbiology
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Natalya B. Perunova
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: perunovanb@gmail.com
PhD, MD (Medicine), Professor, Russian Academy of Sciences
Russian Federation, 11 Pionerskaya St., Orenburg, 460000Oleg V. Bukharin
Institute of Cellular and Intracellular Symbiosis, Orenburg Federal Research Center, Ural Branch, Russian Academy of Sciences
Email: ofrc@list.ru
PhD, MD (Medicine), Full Member, Russian Academy of Sciences, Scientific Director
Russian Federation, 11 Pionerskaya St., Orenburg, 460000References
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