Journal of Translational Medicine | |
Vitamin d deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study | |
Kumar Visvanathan3  Ian Woolley2  Vijaya Sundararajan2  Boyd JG Strauss2  Narelle A Skinner3  Samar Ojaimi1  | |
[1] Department of Infectious Diseases, Southern Health, Clayton Rd, Clayton, Victoria, Australia;Department of Medicine, Southern Clinical School, Monash University, Clayton Rd, Clayton, Victoria, Australia;Departments of Infectious Diseases and Medicine, Clinical Immunology Laboratory, St Vincent’s Hospital, University of Melbourne, 4th Floor, Clinical Sciences Building, Fitzroy, Victoria 3065, Australia | |
关键词: Innate immunity; Immunity; Toll-like receptor; Vitamin D deficiency; Vitamin D; | |
Others : 827066 DOI : 10.1186/1479-5876-11-176 |
|
received in 2013-03-12, accepted in 2013-07-01, 发布年份 2013 | |
【 摘 要 】
Background
Vitamin D is believed to play an important role outside the endocrine system in the regulation of the immune system, and in cellular proliferation and differentiation. The aim of the study was to investigate the impact of vitamin D levels on innate immunity.
Methods
Participants for this prospective, longitudinal study were recruited amongst otherwise healthy staff of a large hospital in Victoria, Australia. Those fulfilling the inclusion criteria, including a vitamin D level of <50 nmol/L, were supplemented. Using flow cytometry, expression of the innate immune receptors TLR2, TLR4 and CD86 was measured on peripheral blood mononuclear cells (PBMCs) collected prior to vitamin D treatment and then at 1 and 3 months. Additonally, PBMCs at each timepoint were stimulated with specific TLR ligands and resultant supernatants were assayed for the cytokines TNFα, IL-6, IFN-α and IP-10.
Results
In participants whose vitamin D level was >100 nmol/L post supplementation (n=11), TLR2 expression on PBMCs increased significantly, with no change noted in TLR4 or CD86 expression. Stimulation of vitamin D deficient samples with TLR ligands produced a number of proinflammatory cytokines, which were significantly reduced upon vitamin D normalisation. In patients whose levels returned to a deficient level at 3 months despite ongoing low-level supplementation, an increase in the pro-inflamamtory state returned. This suggests that vitamin D may play an important role in ensuring an appropriate baseline pro-inflammatory state.
Conclusions
This ex-vivo pilot study adds clinical evidence supporting a possibly important role for vitamin D in innate immunity. If confirmed, this unique clinical study has potentially significant implications for the treatment of a variety of inflammatory conditions, where achieving optimal vitamin D levels may help reduce inflammation.
【 授权许可】
2013 Ojaimi et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140713111928595.pdf | 813KB | download | |
Figure 3. | 94KB | Image | download |
Figure 2. | 23KB | Image | download |
20140710001234935.pdf | 207KB | download |
【 图 表 】
Figure 2.
Figure 3.
【 参考文献 】
- [1]Bickle D: Nonclassic Actions of Vitamin D. J Clin Endocrinol Metab 2009, 94:26-34.
- [2]Holick MF: Vitamin D: Extraskeletal Health. Endocrinol Metab Clin N Am 2010, 39:381-400.
- [3]Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al.: Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010, 9:709-715.
- [4]Binkley N, Ramamurthy R, Krueger D: Low Vitamin D Status: Definition, Prevalence, Consequences, and Correction. Endocrinol Metab Clin N Am 2010, 39:287-301.
- [5]Maalouf NM: The noncalciotropic actions of vitamin D: recent clinical developments. Curr Opin Nephrol Hyperten 2008, 17:408-415.
- [6]Adams JS, Liu PT, Chun R, Modlin RL, Hewison M: VitaminD in Defense of the Human Immune Response. Ann N Y Acad Sci 2007, 1117:94-105.
- [7]Litonjua AA, Weiss ST: Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol 2007, 120:1031-1035.
- [8]Reichrath J: Vitamin D, and the skin: an ancient friend, revisited. Exp Dermatol 2007, 16:618-625.
- [9]Do JE, Kwon SY, Park S, Lee ES: Effects pf vitmain D on expression of Toll-like receptors of monocytes from patients with Behçet’s disease. Rheumatology 2008, 47:840.
- [10]Bekeredjian-Ding I, Jego G: Toll-like receptors - sentries in the B-cell response. Immunology 2009, 128:311-323.
- [11]McCormack WJ, Parker AE, O’Neill LA: Toll-like receptors and NOD-like receptors in Rheumatic Diseases. Arthritis Res & Therapy 2009, 11:243-251. BioMed Central Full Text
- [12]Muzio M, Mantovani A: Toll-like receptors. Microbes and Infection 2000, 2:251-255.
- [13]Rau FC, Dieter J, Luo Z, Priest SO, Baumgarth N: B7-1/2 (CD80/CD86) Direct Signalling to B Cells Enhances IgG Secretion. J Immunol 2009, 183:7661-7671.
- [14]Sadeghi K, Wessner R, Laggner U, Ploder M, Tamandl D, Josef F, et al.: Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular pattern. Eur J Immunol 2006, 36:361-379.
- [15]Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ: Vitamin D: Metabolism. Enodcrinol Metab Clin N Am 2010, 39:243-253.
- [16]Mosekilde L: Vitamin D, requirement and setting recommendation levels: long-term perspectives. Nutr Rev 2008, 66:S170-S177.
- [17]Muscogiuri G, Sorice GP, Prioletta A, Policola C, Della Casa S, Pontecorvi A, et al.: 25-Hydroxyvitamin D Concentration Correlates with Insulin-Sensitivity and BMI in obesity. Obesity 2010, 18:1906-1910.
- [18]Holick MF, Vitamin D: Status: Measurement, Interpretation, and Clinical Application. Ann Epidemiol 2008, 19:73-78.
- [19]Vashi PG, Lammersfeld CA, Braun DP, Gupta D: Serum 25-hydroxyvitamin D is inversely associated with body mass index in cancer. Nutr J 2011, 10:51-57. BioMed Central Full Text
- [20]Konradsen S, Ag H, Lindberg F, Hexeberg S, Jorde R: Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index. Eur J Nutr 2008, 47:87-91.
- [21]Heaney RP: Vitamin D: criteria for safety and efficacy. Nutr Rev 2008, 66:S178-S181.
- [22]Nursyam EW, Amin Z, Rumende CM: The Effect of Vitamin D as Supplementary Treatment in Patients wiht Modertely Advanced Pulmonary Tuberculous lesion. Acta Med Indones 2006, 38:3-5.
- [23]Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al.: High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011, 377:242-250.
- [24]Hollis BW: Assessment and Interpretation of Circulating 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D in the clinical environment. Endocrinol Metab Clin N Am 2010, 39:271-286.
- [25]Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, et al.: Vitamin D-Directed Rheostatic Regulation of Monocyte Antibacterial Responses. J Immunol 2009, 182:4289-4295.
- [26]Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al.: Toll-like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 2006, 311:1770-1773.
- [27]Walker VP, Zhang X, Rastegar I, Liu P, Hollis BW, Adams JS, et al.: Cord Blood Vitamin D Status Impacts Innate Immity Responses. J Endocrinol Metab 2011, 96:1835-1843.
- [28]Bikle DD: Vitamin D, and the immune system: role in protection against bacterial infection. Curr Opin Neprhol Hypertens 2008, 17:348-352.
- [29]Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT: Cytokine profile in patients with Multiple Sclerosis following vitamin D supplementation. J Neuroimmunology 2003, 134:128-132.