Trial reportBMC pulmonary medicine2013
Oral intake of phenylbutyrate with or without vitamin D3 upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis.
Trial report in BMC pulmonary medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01580007 (Clinical Trial of Oral Phenylbutyrate and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis in Bangladesh), which is not on this map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical Trial of Oral Phenylbutyrate and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis in Bangladesh: a Pilot Study
Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1.Nutrients · 2019Trial
- Daily adjunctive therapy with vitamin DJournal of internal medicine · 2018Trial
- Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.PloS one · 2015Trial
- Serum vitamin D and calcium levels among tuberculosis patients in Southern Ethiopia: a comparative cross-sectional study.BMJ open · 2025Article
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- Autophagy in mycobacterial infections: molecular mechanisms, host-pathogen interactions, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2025Review
- Repurposed Drugs and Plant-Derived Natural Products as Potential Host-Directed Therapeutic Candidates for Tuberculosis.Biomolecules · 2024Review
- Comparative Study of Vitamin D Levels in Newly Diagnosed Tuberculosis and a Normal Population.Medicina (Kaunas, Lithuania) · 2024Article
- The Interplay betweenClinics and practice · 2024Review
- aSynPEP-DB: a database of biogenic peptides for inhibiting α-synuclein aggregation.Database : the journal of biological databases and curation · 2023Article
- Vitamin D as a Shield against Aging.International journal of molecular sciences · 2023Review
- The gut microbiome: A line of defense against tuberculosis development.Frontiers in cellular and infection microbiology · 2023Review
- In Vitro, In Vivo and In Silico Assessment of the Antimicrobial and Immunomodulatory Effects of a Water Buffalo Cathelicidin (WBCATH) in Experimental Pulmonary Tuberculosis.Antibiotics (Basel, Switzerland) · 2022Article
- Vitamin D supplementation and immune-related markers: an update from nutrigenetic and nutrigenomic studies.The British journal of nutrition · 2022Review
- Insights into innovative therapeutics for drug-resistant tuberculosis: Host-directed therapy and autophagy inducing modified nanoparticles.International journal of pharmaceutics · 2022Article
- The effect of gum Arabic supplementation on cathelicidin expression in monocyte derived macrophages in mice.BMC complementary medicine and therapies · 2022Article
- Association of household air pollution with cellular and humoral immune responses among women in rural Bangladesh.Environmental pollution (Barking, Essex : 1987) · 2022Article
- Impact of Vitamin D in Prophylaxis and Treatment in Tuberculosis Patients.International journal of molecular sciences · 2022Review
- Article
- Host Defense Peptides at the Ocular Surface: Roles in Health and Major Diseases, and Therapeutic Potentials.Frontiers in medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe earlier showed that 4-phenylbutyrate (PB) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D3 in a lung epithelial cell line. We aimed to evaluate a therapeutic dose of PB alone or in combination with vitamin D3 for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (MDM).
methodsHealthy volunteers were enrolled in an 8-days open trial with three doses of PB [250 mg (Group-I), 500 mg (Group-II) or 1000 mg (Group-III)] twice daily (b.d.) together with vitamin D3 {5000 IU once daily (o.d.)}, PB (500 mg b.d.) (Group-IV) or vitamin D3 (5000 IU o.d.) (Group-V), given orally for 4 days. Blood was collected on day-0, day-4 and day-8; plasma was separated, peripheral blood mononuclear cells (PBMC), non-adherent lymphocytes (NAL) and MDM were cultured. LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA, respectively. In plasma, 25-hydorxyvitamin D3 levels were determined by ELISA. MDM-mediated killing of Mycobacterium tuberculosis (Mtb) (H37Rv) was performed by conventional culture method.
resultsMDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4, while Group-I showed increased transcript at day-4 and day-8 compared to day-0 (p < 0.05). Both Group-I and -II exhibited higher levels of transcript on day-4 compared to Group-III and Group-V (p < 0.035). Increased induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV (p < 0.05), while Group-IV showed increased levels on day-8 compared to Group-I and Group-III (p < 0.04). Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I, -II and -V (p < 0.05).
conclusionThe results demonstrate that 500 mg b.d. PB with 5000 IU o.d. vitamin D3 is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages. Hence, this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB (NCT01580007).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.