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Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy

Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy


Titill: Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy
Höfundur: Rekha, Rokeya Sultana
Mily, Akhirunnesa
Sultana, Tajnin
Haq, Ahsanul
Ahmed, Sultan
Mostafa Kamal, S. M.
van Schadewijk, Annemarie
Hiemstra, Pieter S.
Guðmundsson, Guðmundur H.
Agerberth, Birgitta
... 1 fleiri höfundar Sýna alla höfunda
Útgáfa: 2018-07-04
Tungumál: Enska
Umfang: 303
Háskóli/Stofnun: Háskóli Íslands
University of Iceland
Svið: Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Deild: Lífvísindasetur (HÍ)
Biomedical Center (UI)
Birtist í: BMC Infectious Diseases;18(1)
ISSN: 1471-2334
DOI: 10.1186/s12879-018-3203-9
Efnisorð: Mycobacterium tuberculosis; Cytokines; Chemokines; Endoplasmic reticulum stress; Human beta-defensin-1 (HBD1); Berklar; Smitsjúkdómar; Frumulíffræði; D vítamín
URI: https://hdl.handle.net/20.500.11815/878

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Tilvitnun:

Rekha, R. S., Mily, A., Sultana, T., Haq, A., Ahmed, S., Mostafa Kamal, S. M., . . . Raqib, R. (2018). Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy. BMC Infectious Diseases, 18(1), 303. doi:10.1186/s12879-018-3203-9

Útdráttur:

Background We have previously shown that 8 weeks’ treatment with phenylbutyrate (PBA) (500mgx2/day) with or without vitamin D3 (vitD3) (5000 IU/day) as host-directed therapy (HDT) accelerated clinical recovery, sputum culture conversion and increased expression of cathelicidin LL-37 by immune cells in a randomized, placebo-controlled trial in adults with pulmonary tuberculosis (TB). In this study we further aimed to examine whether HDT with PBA and vitD3 promoted clinically beneficial immunomodulation to improve treatment outcomes in TB patients. Methods Cytokine concentration was measured in supernatants of peripheral blood mononuclear cells (PBMC) from patients (n = 31/group). Endoplasmic reticulum stress-related genes (GADD34 and XBP1spl) and human beta-defensin-1 (HBD1) gene expression were studied in monocyte-derived-macrophages (MDM) (n = 18/group) from PBMC of patients. Autophagy in MDM (n = 6/group) was evaluated using LC3 expression by confocal microscopy. Results A significant decline in the concentration of cytokines/chemokines was noted from week 0 to 8 in the PBA-group [TNF-α (β = − 0.34, 95% CI = − 0.68, − 0.003; p = 0.04), CCL11 (β = − 0.19, 95% CI = − 0.36, − 0.03; p = 0.02) and CCL5 (β = − 0.08, 95% CI = − 0.16, 0.002; p = 0.05)] and vitD3-group [(CCL11 (β = − 0.17, 95% CI = − 0.34, − 0.001; p = 0.04), CXCL10 (β = − 0.38, 95% CI = − 0.77, 0.003; p = 0.05) and PDGF-β (β = − 0.16, 95% CI = − 0.31, 0.002; p = 0.05)] compared to placebo. Both PBA- and vitD3-groups showed a decline in XBP1spl mRNA on week 8 (p < 0.03). All treatment groups demonstrated increased LC3 expression in MDM compared to placebo over time (p < 0.037). Conclusion The use of PBA and vitD3 as adjunct therapy to standard TB treatment promoted favorable immunomodulation to improve treatment outcomes.

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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

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