Vitamin D

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D- a randomized, double blind, placebo-controlled study

Cytokine 2015 Feb 30;71(2):132-8. Epub 2014 Oct 30.

Tyler Barker, Victoria E Rogers, Mark Levy, Jenna Templeton, Howard Goldfine, Erik D Schneider, Brian M Dixon, Vanessa T Henriksen, Lindell K Weaver

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The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D.

Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ≈29%; 8000IU, ≈57%) and 1,25(OH)D (4000IU, ≈12%; 8000IU, ≈38%) without altering intact parathyroid hormone or calcium.

The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation.

Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D⩾30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D.

Affiliation

Hyperbaric Medicine, Intermountain Medical Center, Murray, UT 84107, USA; LDS Hospital, Salt Lake City, UT 84143, USA; School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.

PLoS ONE 2015-01-01

Vitamin D regulates cytokine patterns secreted by dendritic cells to promote differentiation of IL-22-producing T cells.

Andrea Sommer, Mario Fabri


PMID 26107738

Abstract

One central mechanism, by which vitamin D regulates human immune responses, is the direct modulation of dendritic cells (DCs). However, the effect of vitamin D on several key DC functions, such as the secretion of central inflammatory cytokines, remains controversial. Moreover, whether vitamin D treatment of DCs regulates their ability to promote differentiation of IL-17-/IL-22-producing T cell subsets, such as Th17 and Th22 cell, is not known.

Here, we report that vitamin D treatment during differentiation of monocytes into DCs markedly enhanced their ability to secrete TNF-α, IL-6, IL-1β and IL-23. Cytokines secreted by vitamin D-treated DC were significantly more potent in driving differentiation of IL-22-producing T cells, but not IL-17-producing T cells, as compared to secreted cytokines of not-vitamin D-treated DCs.

Finally, we found that the differentiation of IL-22-producing T cells mediated by supernatants of vitamin D-treated DCs was dependent on TNF-α IL-6 and IL-23. In summary, our study suggests a novel role of vitamin D in regulating DC-mediated immune responses in humans.

Zhonghua Nei Ke Za Zhi. 2015 Apr;54(4):317-21.

[1,25(OH)2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis]

[Article in Chinese]

Wen H1, Luo J2, Zhang X2, Zhang C2, Zhao X2, Wang X2, Li X2.

Author information

  • 1Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China; Email: wenhongyan0509@aliyun.com.

  • 2Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

Abstract

OBJECTIVE:

To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA).

METHODS:

Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)₂D₃and methotrexate (MTX). After co-culture, the serum levels of Th17 cytokines interleukin (IL)-17, IL-6, tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA). The level of IL-22 was analyzed by enzyme-linked immunosorbent assay (ELISA). The independent samples t test and one-way analysis of variance (ANOVA) were used for statistical analysis.

RESULTS:

The levels of cytokines IL-17, TNFα, IL-6 and IL-22 in RA group were significantly higher than those in the control group [(43 ± 6)ng/L, (5.91 ± 2.53)ng/L, (16.6 ± 12.0)ng/L, (51 ± 17)ng/L vs (21 ± 3)ng/L, (2.63 ± 0.27)ng/L, (4.2±2.3)ng/L, (22 ± 14)ng/L]. Each of the three different 1,25(OH)₂D₃doses inhibited secretion of IL-17[(533 ± 47) pg/ml, (426 ± 55)pg/ml, (319 ± 86)pg/ml], TNFα[(424 ± 82)pg/ml, (382 ± 79)pg/ml, (326 ± 87)pg/ml], and IL-6[(5 513 ± 3 429)pg/ml, (4 555 ± 3 157)pg/ml, (3 748 ± 1 919)pg/ml] in RA group (P < 0.05), yet no statistical difference was found in IL-22 secretion with a trend of decrease after treatment of 1,25(OH)₂D₃. Three different doses of MTX inhibited secretion of IL-17 [(452 ± 50) pg/ml, (372 ± 67) pg/ml, (315 ± 104)pg/ml] and TNFα [(319 ± 74)pg/ml, (292 ± 59)pg/ml, (266 ± 64)pg/ml] in RA group (P < 0.05).However, levels of IL-6 and IL-22 were not affected after treated with MTX.

CONCLUSION:

Our data indicated that 1,25(OH)₂D₃may play as an immune modulating agent to suppress Th17 cell cytokines. Supplement of vitamin D has the effective potential to treat patients with RA or other Th17 cell mediated autoimmune disorders.

 

Brain Inj. 2015 Jun 17:1-10. [Epub ahead of print]

Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury

Tang H1, Hua F, Wang J, Yousuf S, Atif F, Sayeed I, Stein DG.

Author information

  • 1Department of Emergency Medicine, Emory University , Atlanta, GA , USA.

Abstract

OBJECTIVE:

Inflammation is an important component of the response to traumatic brain injury (TBI). Progesterone has been shown to inhibit neuroinflammation following (TBI) and may do so through Toll-like receptor (TLR)-mediated pathways. In vitro studies indicate that 1,25-dihydroxyvitamin D(3) (VDH) may also modulate the inflammatory response through the TLR4 pathway. This study tested the hypothesis that PROG and VDH would exert additive and synergistic neuroprotective effects compared with individual treatment by modulating TLR4/NF-κB-mediated inflammation pathways after TBI in rats.

RESEARCH DESIGN AND METHODS:

Bilateral medial frontal cortical impact injury was induced in young adult Sprague-Dawley rats. Progesterone (i.p., 16 mg kg-1 body weight) and VDH (1 µg kg-1 body weight) were injected separately or combined at 1 and 6 hours after surgery. Rats were killed 24 hours post-surgery and peri-contusional brain tissue harvested for immunostaining and protein measurement.

RESULTS:

TLR4, phosphorylation of NF-κB, neuronal loss and astrocyte activation were significantly reduced with combination treatment after TBI compared to each agent given individually.

CONCLUSIONS:

At 24 hours after TBI, combination therapy shows greater efficacy in reducing neuroinflammation compared to progesterone and VDH given separately, and does so by modulating the TLR4/NF-κB signalling pathway.

J Neurol Sci. 2015 Mar 15;350(1-2):18-23. doi: 10.1016/j.jns.2015.01.030. Epub 2015 Jan 28.

Interleukin-10 but not transforming growth factor-β1 gene expression is up-regulated by vitamin D treatment in multiple sclerosis patients

Farsani ZS1, Behmanesh M2, Sahraian MA3.

Author information

  • 1Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

  • 2Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: behmanesh@modares.ac.ir.

  • 3MS Research Center, Neuroscience Institute, Tehran University of Medical Science, Tehran, Iran.

Abstract

Multiple sclerosis (MS) is an inflammatory and autoimmune disease. Variety of different genetics and environmental factors are involved in MS pathology. The epidemiological studies demonstrated that vitamin D has immune and immunomodulating effects on MS disease. Therefore, this study aims to evaluate the effect of vitamin D treatment on the expression of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) genes in MS patients.

We found that, the expression level of IL-10 gene in treated patients was up-regulated 3.84 times more than before treatment, but the expression level of TGF-β1 was not affected by vitamin D treatment. Also, a significant relationship was observed between vitamin D level and EDSS in MS patients.

Our results indicated that the increased level of serum vitamin D and IL-10 gene expression may be associated with the reduction of EDSS scores in MS patients.

J Neuroimmunol. 2015 Aug 15;285:125-8. doi: 10.1016/j.jneuroim.2015.05.022. Epub 2015 Jun 12.

Effect of high dose vitamin D intake on interleukin-17 levels in multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial

Toghianifar N1, Ashtari F2, Zarkesh-Esfahani SH3, Mansourian M4.

Author information

  • 1Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: n.toghiani@gmail.com.

  • 2Isfahan University of Medical Sciences, Isfahan, Iran; Isfahan Neuroscience Research Centre, Iran.

  • 3University of Isfahan, Department of Biology, Isfahan, Iran.

  • 4Department of Biostatistics and Epidemiology, Health School, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

BACKGROUND:

Vitamin D has immunomodulatory effects in multiple sclerosis (MS). Vitamin D acts through various mechanisms such as secretion of cytokines. Interleukin-17 (IL-17) is a critical interleukin in inflammatory response in MS.

OBJECTIVE:

This study assessed the effect of oral high dose vitamin D intake on IL-17 levels in MS patients in a double blind randomized clinical trial.

METHODS:

94 patients with a diagnosis of relapsing remitting multiple sclerosis (RRMS) were randomized to two groups.

One group received 50,000 IU vitamin D3 every five days for 12 weeks. The other group was given placebo. Both groups received interferon-β (IFN-β) treatment. Serum levels of IL-17 were measured at the beginning of the study and after 12weeks.

RESULTS:

IL-17 serum levels were 56.75±28.72pg/ml and 30.31±75.85pg/ml in the intervention and placebo group at the beginning of the study, respectively (Median±IQR, p=0.338). After 12weeks, IL-17 levels were 58.93±67.93pg/ml and 46.13±94.70pg/ml in the intervention and placebo group, respectively (Median±IQR, p=0.960). The multiple linear regression analysis indicated that the consumption of vitamin D3 was positively and significantly associated with the logarithm of IL-17 measures (β=1.719; p=0.002 and R2=0.91), adjusted by EDSS scores.

CONCLUSION:

IL-17 levels showed significant change in RRMS patients after receiving high dose vitamin D3 for 12weeks.

PLoS One. 2015 Jun 24;10(6):e0130395. doi: 10.1371/journal.pone.0130395. eCollection 2015.

Vitamin D regulates cytokine patterns secreted by dendritic cells to promote differentiation of IL-22-producing T cells

Sommer A1, Fabri M1.

Author information

  • 1Department of Dermatology, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.

Abstract

One central mechanism, by which vitamin D regulates human immune responses, is the direct modulation of dendritic cells (DCs). However, the effect of vitamin D on several key DC functions, such as the secretion of central inflammatory cytokines, remains controversial. Moreover, whether vitamin D treatment of DCs regulates their ability to promote differentiation of IL-17-/IL-22-producing T cell subsets, such as Th17 and Th22 cell, is not known.

Here, we report that vitamin D treatment during differentiation of monocytes into DCs markedly enhanced their ability to secrete TNF-α, IL-6, IL-1β and IL-23. Cytokines secreted by vitamin D-treated DC were significantly more potent in driving differentiation of IL-22-producing T cells, but not IL-17-producing T cells, as compared to secreted cytokines of not-vitamin D-treated DCs. Finally, we found that the differentiation of IL-22-producing T cells mediated by supernatants of vitamin D-treated DCs was dependent on TNF-α IL-6 and IL-23.

In summary, our study suggests a novel role of vitamin D in regulating DC-mediated immune responses in humans.

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