cholecalciferol and Tuberculosis

Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity.. Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients.. A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review.. The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant.. The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Topics: Blood Glucose; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Tuberculosis; Tuberculosis, Pulmonary; Vitamin D

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).

Topics: Arthritis, Rheumatoid; Cholecalciferol; Coronary Artery Disease; Diabetes Mellitus; Ergocalciferols; Female; Genetic Predisposition to Disease; Humans; Male; Neoplasms; Obesity; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Tuberculosis; Vitamin D-Binding Protein

Vitamin D(3) affects both the innate as well as adaptive immune responses. Epidemiological studies have established that vitamin D(3) deficiency plays an important role in tuberculosis (TB) and viral influenza prevalence as well as susceptibility to active disease in TB. Vitamin D(3) status has been associated with the clinical course of HIV infection and drug interaction with anti-retroviral therapy. This article reviews the immunomodulatory capacity of vitamin D(3) and examines the impact of vitamin D(3) supplementation as a preventive or therapeutic intervention with the intent to uncover its potential therapeutic application in infectious diseases and to identify novel areas for future research. We present a review of randomized, controlled clinical studies conducted in humans which included assessment of the immune function or clinical outcome as study end points. Current data support vitamin D(3) supplementation as risk-modifying intervention in tuberculosis and viral respiratory tract infection, but the optimal dosage regimen remains to be determined. However, to date the knowledge on its role in fungal infection and sepsis is limited although a potential benefit could be harnessed from its ability to curtail the unrestrained pro-inflammatory response and therefore prevent excessive collateral tissue damage.

Topics: Cholecalciferol; Communicable Disease Control; Communicable Diseases; Humans; Immunologic Factors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Tuberculosis

Autophagy is a vital homeostatic process triggered by starvation and other cellular stresses, in which cytoplasmatic cargo is targeted for degradation in specialized structures termed autophagosomes. Autophagy is involved in nutrient regeneration, protein and organelle degradation, but also in clearance of intracellular pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Recent studies suggest that induction of autophagy in macrophages is an effective mechanism to enhance intracellular killing of M. tuberculosis, and that the ability of the pathogen to inhibit this process is of paramount importance for its survival. Patient studies have shown genetic associations between tuberculosis and the autophagy gene IRGM, as well as with several genes indirectly involved in autophagy. In this review we will discuss the complex interplay between M. tuberculosis and autophagy, as well as the effect of polymorphisms in autophagy-related genes on susceptibility to tuberculosis.

Topics: Autophagy; Case-Control Studies; Cholecalciferol; Cytokines; Gene Frequency; Genetic Predisposition to Disease; GTP-Binding Proteins; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Tuberculosis; Tumor Necrosis Factor-alpha

The innate immune system provides the host with an immediate and rapid defense against invading microbes. Detection of foreign invaders is mediated by a class of receptors that are known as the pattern recognition receptors, such as the family of Toll-like receptors (TLRs). In humans, ten functional TLRs have been identified and they respond to conserved pathogen-associated molecular patterns derived from bacteria, mycoplasma, fungi and viruses. TLR activation leads to direct antimicrobial activity against both intracellular and extracellular bacteria, and induces an antiviral gene program. Recently, it was reported that TLR2 activation leads to the use of vitamin D3 as a mechanism to combat Mycobacterium tuberculosis. Here, we focus on recent findings concerning the TLR-induced antimicrobial mechanisms in humans and the therapeutic implications of these findings. Owing to their capability to combat a wide array of pathogens, TLRs are attractive therapeutic targets. However, additional knowledge about their antimicrobial mechanisms is needed.

Topics: Animals; Cholecalciferol; Humans; Immunity, Innate; Mycobacterium tuberculosis; Receptors, Calcitriol; Toll-Like Receptor 2; Tuberculosis

Topics: Animals; Cholecalciferol; Disease Models, Animal; Drug Resistance, Multiple; Humans; Immunotherapy; Interferon-gamma; Macrophages; Mice; Mycobacterium tuberculosis; Tuberculosis

To determine whether weekly oral supplementation with 10,000 IU vitamin D. We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect.. Weekly oral supplementation with 10,000 IU vitamin D

Topics: Child; Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Latent Tuberculosis; Mycobacterium tuberculosis; South Africa; Tuberculosis; Vitamin D; Vitamins

We 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).. Healthy 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.. MDM 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).. The 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).

Topics: Administration, Oral; Adolescent; Adult; Antimicrobial Cationic Peptides; Antineoplastic Agents; Calcium; Cathelicidins; Cells, Cultured; Cholecalciferol; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Immunity, Innate; Macrophages; Male; Middle Aged; Mycobacterium tuberculosis; Phenylbutyrates; RNA, Messenger; Tuberculosis; Up-Regulation; Vitamins; Young Adult

Concurrent infection with COVID-19 and. Since morphoproteomics combines the disciplines of histopathology, molecular biology and protein chemistry to paint a portrait of the protein circuitry in diseased cells for the purpose of uncovering targets amenable to specific intervention [1], we used morphoproteomic analyses to study lung tissues of patients with early post-primary tuberculosis or COVID-19 infection.. These studies showed co-localization of the COVID-19 virus and. The commonalities in these pathways suggest that they might be susceptible to adjunctive therapies with metformin and vitamin D3. This is supported by published studies that metformin and vitamin D3 could reduce the severity of both COVID-19 and early post-primary TB infections.

Topics: Cholecalciferol; COVID-19; Humans; Lung; Mycobacterium tuberculosis; Tuberculosis

Topics: Cholecalciferol; Dietary Supplements; Double-Blind Method; HIV Infections; Humans; Tuberculosis; Tuberculosis, Pulmonary

Vitamin D

Topics: Animals; Bacterial Load; Cells, Cultured; Cholecalciferol; Cytokines; Dietary Supplements; Disease Models, Animal; Ethanol; Female; Host-Pathogen Interactions; Macrophages; Mice, Inbred C57BL; Mycobacterium bovis; Tuberculosis; Vitamin D Deficiency

Topics: Cholecalciferol; Ethiopia; Humans; Phenylbutyrates; Tuberculosis; Tuberculosis, Pulmonary; Vitamin D

Mycobacterium tuberculosis (Mtb) is a highly infectious aerosolizable bacterium, which causes upward of 1.5 million deaths per year. Alveolar macrophages, the primary defense cell of the lung, are the preferred host cell of this intracellular bacterium. Vitamin D

Topics: Animals; Cell Line; Cholecalciferol; Hydrogen Peroxide; Macrophages; Mice; Models, Theoretical; Mycobacterium tuberculosis; NADPH Oxidases; Tuberculosis

Mycobacterium tuberculosis ( Mtb), is a highly infectious airborne bacterium. Previous studies have found vitamin D

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Autophagy; Bacterial Load; Cell Line; Cholecalciferol; Interleukin-12; Macrophages; Mice; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nitric Oxide; Signal Transduction; Tuberculosis

Immune-modulating drugs that target myeloid-derived suppressor cells or stimulate natural killer T cells have been shown to reduce mycobacterial loads in tuberculosis (TB). We aimed to determine if a combination of these drugs as adjunct immunotherapy to conventional antibiotic treatment could also increase therapeutic efficacy against TB. In our model of pulmonary TB in mice, we applied treatment with isoniazid, rifampicin, and pyrazinamide for 13 weeks alone or combined with immunotherapy consisting of all-trans retinoic acid, 1,25(OH)

Topics: Animals; Anti-Bacterial Agents; Antitubercular Agents; Cholecalciferol; Combined Modality Therapy; Disease Models, Animal; Female; Galactosylceramides; Immunity, Cellular; Immunotherapy; Lung; Mice, Inbred BALB C; Recurrence; Tretinoin; Tuberculosis; Tumor Necrosis Factor-alpha

The aim of this study was to estimate the concentration of cholecalciferol and 13-cis-retinoic acid (RA) in the plasma and pleural fluid of patients with tuberculosis (TB) against controls.. Plasma levels of cholecalciferol and 13-cis-RA were measured in 22 patients with TB and healthy controls and their pleural fluids levels were measured in 6 TB patients and diseased controls by established high-performance liquid chromatography-based procedure.. Cholecalciferol levels in plasma and pleural fluid of patients with TB and healthy controls were 67.45 (10.71) nmol/L and 21.40 (8.58) nmol/L compared with 117.43 (18.40) nmol/L (P < 0.001) and 94.73 (33.34) nmol/L (P = 0.0049), respectively. 13-cis-RA level in the plasma of patients with TB and healthy controls were 1.51 (0.72) nmol/L and 6.67 (0.81) nmol/L (P < 0.001), respectively. 13-cis-RA was not detectable in pleural fluid. The levels of both the agents were lower in patients with TB than in controls.. It was observed that in patients with TB there is a combined deficiency of cholecalciferol and 13-cis-RA compared with healthy volunteers. Because cholecalciferol and 13-cis-RA are in equilibrium with active ingredients of vitamins A and D, we feel that there is a combined deficiency of these vitamins in patients with TB. There is an evidence that concomitant vitamin A and D supplementation can kill intracellular Mycobacterium tuberculosis in vitro. Therefore, the observations made in this study can pave the path for a trial of combined supplementation of available formulations of vitamin A and D (cholecalciferol and 13-cis-RA) for novel anti-tubercular drug therapy. Because such an approach is host-based it has potential to treat even multidrug-resistant and extensively drug-resistant forms of TB.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Cholecalciferol; Dietary Supplements; Drug Resistance, Multiple, Bacterial; Female; Humans; Isotretinoin; Male; Middle Aged; Mycobacterium tuberculosis; Tuberculosis; Vitamin A Deficiency; Vitamin D Deficiency; Young Adult

Topics: Cholecalciferol; Humans; Tuberculosis; Vitamin D; Vitamin D Deficiency

Recent discoveries have revealed the importance of the vitamin D-dependent generation of antimicrobial peptides in human host defense against Mycobacterium tuberculosis. Now, Yuk et al. (2009) show how vitamin D induces autophagy and mediates colocalization of Mycobacterium tuberculosis and antimicrobial peptides within an autophagolysosome, leading to killing of the bacterium.

Topics: Autophagy; Cholecalciferol; Humans; Mycobacterium tuberculosis; Tuberculosis

Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular Mycobacterium tuberculosis. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.

Topics: Antimicrobial Cationic Peptides; Autophagy; Cathelicidins; Cells, Cultured; Cholecalciferol; Host-Pathogen Interactions; Humans; Macrophages; Monocytes; Mycobacterium tuberculosis; Tuberculosis

Topics: Cholecalciferol; Genotype; Humans; Receptors, Calcitriol; Tuberculosis; Vitamin D; Vitamin D Deficiency

Vitamin D metabolites have several biologic functions besides the best-known one of controlling mineral metabolism, one of which may be protection against tuberculosis. The chemical structures of the metabolites govern their functions. The most potent metabolite for regulating calcium metabolism is 1,25(OH)2-vitamin D3 (1,25-D3). This metabolite also is able to protect cultured human monocytes and macrophages (MP) against tubercle bacilli (TB). To determine whether these two functions are connected, 14 other analogs or metabolites of vitamin D were compared with 1,25-D3 for ability to protect cultured MP against TB. Blood-derived MP from 18 different donors were used in 70 experiments. The MP were infected with TB, then incubated for 7 days in medium containing 4 micrograms/ml of metabolite or synthesized analog. Growth of TB in the MP was measured by colony-forming unit counts from samples of lysed MP at 0, 4, and 7 days after infection. The metabolites, none of which inhibited TB in the absence of MP, varied from unprotective to bacteriostatic in the MP. Four of them were nearly as protective as 1,25-D3, and the metabolite 25S, 26(OH)2-vitamin D3 was consistently more protective. An analog synthetically designed for maximum ability to promote cell differentiation was unprotective. There was no correlation between metabolite ability to protect and known ability to stimulate calcium mobilization. These results suggest that antituberculosis protection of human MP by vitamin D metabolites or analogs can be separated from their functions of inducing cell differentiation and controlling mineral metabolism.

Topics: Adult; Calcitriol; Cells, Cultured; Cholecalciferol; Female; Humans; Macrophages; Male; Middle Aged; Tuberculosis; Vitamin D

Topics: Calcitriol; Calcium; Cholecalciferol; Epidemiologic Methods; Extracellular Space; Homeostasis; Humans; Immune System; Immunity; India; Tuberculosis; United Kingdom; Vitamin D; Vitamin D-Binding Protein