| Title |
Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy
|
|---|---|
| Published in |
BMC Infectious Diseases, July 2018
|
| DOI | 10.1186/s12879-018-3203-9 |
| Pubmed ID | |
| Authors |
Rokeya Sultana Rekha, Akhirunnesa Mily, Tajnin Sultana, Ahsanul Haq, Sultan Ahmed, S. M. Mostafa Kamal, Annemarie van Schadewijk, Pieter S. Hiemstra, Gudmundur H. Gudmundsson, Birgitta Agerberth, Rubhana Raqib |
| Abstract |
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. 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. 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). The use of PBA and vitD3 as adjunct therapy to standard TB treatment promoted favorable immunomodulation to improve treatment outcomes. This trial was retrospectively registered in clinicaltrials.gov, under identifier NCT01580007 . |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 17% |
| France | 1 | 17% |
| Bangladesh | 1 | 17% |
| United Kingdom | 1 | 17% |
| Unknown | 2 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
| Scientists | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 93 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 11 | 12% |
| Student > Bachelor | 11 | 12% |
| Researcher | 10 | 11% |
| Lecturer | 7 | 8% |
| Student > Postgraduate | 6 | 6% |
| Other | 20 | 22% |
| Unknown | 28 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 23 | 25% |
| Immunology and Microbiology | 9 | 10% |
| Biochemistry, Genetics and Molecular Biology | 8 | 9% |
| Agricultural and Biological Sciences | 7 | 8% |
| Nursing and Health Professions | 4 | 4% |
| Other | 8 | 9% |
| Unknown | 34 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2020.
All research outputs
#13,621,195
of 23,094,276 outputs
Outputs from BMC Infectious Diseases
#3,418
of 7,751 outputs
Outputs of similar age
#169,952
of 328,026 outputs
Outputs of similar age from BMC Infectious Diseases
#61
of 162 outputs
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