The Open Rheumatology Journal




ISSN: 1874-3129 ― Volume 13, 2019
EDITORIAL

The Enigma of Vitamin D Role in Inflammation



Mattia Bellan1, Alessandra Nerviani2, Pier Paolo Sainaghi3
1 Department of Translational Medicine Università del Piemonte Orientale UPO via Solaroli 17 Novara (NO), 28100 Italy, Division of Internal Medicine Sant’Andrea Hospital Vercelli, Italy and IRCAD Interdisciplinary Research Center of Autoimmune Diseases Novara Italy, Tel: +390321-3733966 E-mail: bellanmattia@yahoo.it
2 Experimental Medicine and Rheumatology William Harvey Research Institute and Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK and IRCAD Interdisciplinary Research Center of Autoimmune Diseases Novara Italy
3 Immuno-rheumatology Outpatien Unit AOU Maggiore della Carità Novara Italy and IRCAD Interdisciplinary Research Center of Autoimmune Diseases Novara Italy


Article Information


Identifiers and Pagination:

Year: 2018
Volume: 12
Issue: Suppl-1, M1
First Page: 197
Last Page: 200
Publisher Id: TORJ-12-197
DOI: 10.2174/1874312901812010197

Article History:

Electronic publication date: 27/12/2018
Collection year: 2018

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 368
Abstract HTML Views: 273
PDF Downloads: 191
ePub Downloads: 162
Total Views/Downloads: 994

Unique Statistics:

Full-Text HTML Views: 196
Abstract HTML Views: 162
PDF Downloads: 122
ePub Downloads: 101
Total Views/Downloads: 581
Geographical View

© 2018 Bellan et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.







Vitamin D is a widely studied molecule, but several aspects of its biologic behaviour remain unclear. Despite having been considered for decades solely as a co-actor of the bone metabolism regulation, multiple experimental observations have suggested a role in different fields of human physiology [1Gil Á, Plaza-Diaz J, Mesa MD. Vitamin D: Classic and novel actions. Ann Nutr Metab 2018; 72(2): 87-95.[http://dx.doi.org/10.1159/000486536] [PMID: 29346788] ]. Notably, numerous authors attributed to vitamin D key functions in the regulation of the immune system [2Bikle DD. Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin Nephrol Hypertens 2008; 17(4): 348-52.[http://dx.doi.org/10.1097/MNH.0b013e3282ff64a3] [PMID: 18660668] -12Zhang H, Shih DQ, Zhang X. Mechanisms underlying effects of 1,25-Dihydroxyvitamin D3 on the Th17 cells. Eur J Microbiol Immunol (Bp) 2013; 3(4): 237-40.[http://dx.doi.org/10.1556/EuJMI.3.2013.4.1] [PMID: 24294492] ], hence revealing its potential contribution in the management of inflammatory diseases [13Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis: Results from the Iowa Women’s Health Study. Arthritis Rheum 2004; 50(1): 72-7.[http://dx.doi.org/10.1002/art.11434] [PMID: 14730601] -22Chandrashekara S, Patted A. Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study. Int J Rheum Dis 2017; 20(7): 825-31.[http://dx.doi.org/10.1111/1756-185X.12770] [PMID: 26481198] ].

However, as well as for other promising molecules under investigation, a significant gap between the strength of the in vitro data and the weakness of the in vivo observations still exists. There are several reasons beyond this discrepancy: for instance, experimental conditions in vitro cannot replicate the complex regulation of the vitamin D-dependent pathways in vivo; moreover, vitamin D concentrations used in vitro are generally significantly higher than those physiologically measured in human subjects. To date, the real and actual impact of the vitamin D status on inflammation in vivo is still an enigma. Consequently, whether or not vitamin D plays a relevant role in the development and management of inflammatory diseases is still a matter of debate. If, on the one side, we should not neglect vitamin D potentialities, on the other side, we must avoid considering it a “panacea”, as this misinterpretation might lead to overtreatment with direct and indirect relevant costs [23Glade MJ. Vitamin D: Health panacea or false prophet? Nutrition 2013; 29(1): 37-41.[http://dx.doi.org/10.1016/j.nut.2012.05.010] [PMID: 23085014] , 24Cianferotti L, Bertoldo F, Bischoff-Ferrari HA, et al. Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: Research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO). Endocrine 2017; 56(2): 245-61.[http://dx.doi.org/10.1007/s12020-017-1290-9] [PMID: 28390010] ].

A large-scale screening and supplementation strategies for therapeutic indications other than the maintenance of bone homeostasis are currently not supported by the available evidence, and their clinical advantage and cost-effectiveness are doubtful.

In this special issue, contributions from eminent figures in this field have been gathered to try to elucidate what we already know and what is new about vitamin D and inflammation.

At first, Trombetta and colleagues [25Trombetta AC, Paolino S, Cutolo M. Vitamin d, inflammation and immunity: Review of literature and considerations on recent translational and clinical research developments The Open Rheumatol J 2018; 12: 201-13.] extensively and comprehensively revised the current knowledge about the in vivo and in vitro vitamin D activity on the immune system regulation and its implications for the development of autoimmune diseases. To deepen the insights on specific pathological conditions, Nerviani et al. [26Nerviani A, Mauro D, Gilio M, Grembiale RD, Lewis M. To supplement or not to supplement? The rationale of vitamin D supplementation in systemic lupus erythematosus. The Open Rheumatol J 2018; 12: 214-25.] reviewed the relevant literature about the impact of the vitamin D status on the clinical course of Systemic Lupus Erythematosus (SLE). In this manuscript, the authors presented the available data assessing the effects of vitamin D on several markers of disease activity, further discussing the evidence supporting a role for vitamin D supplementation in the management of SLE. The specific relationship with the antiphospholipid antibody syndrome has been revised in depth by Gualtierotti and colleagues [27Gualtierotti R, Di Giacomo A, Raschi E, Borghi MO, Meroni PL. Vitamin D and anti-phospholipid antibody syndrome. The Open Rheumatol J 2018; 12: 226-47.], who also included original data showing the in vitro effects of vitamin D supplementation on the endothelial perturbation in this condition.

In the context of inflammatory arthritis, Crotti and colleagues [28Crotti C, Becciolini A, Biggioggero M, Favalli EG. Vitamin D and spondyloarthritis: Review of the literature. The Open Rheumatol J 2018; 12: 248-60.] discussed the current evidence about the role of vitamin D in the development of spondyloarthritis; here the authors not only underpinned the discrepancies existing in this field, but also stressed the relevance that vitamin D status seems to have in the occurrence of some critical co-morbidities in the course of systemic inflammatory diseases.

Resulting from the impairment of several biological pathways involved in the bone metabolism, osteoporosis and increased risk of fracture are common in inflammatory arthritis. Bone health and immune system are strictly related, and their complex and intriguing connections are the matter of study of a recently developed field known as “osteoimmunology”. In this regards, Sainaghi and Gibbin [29Sainaghi PP, Gibbin A. Vitamin D, inflammation and Osteoporosis in Rheumatoid Arthritis. The Open Rheumatol J 2018; 12: 261-78.] reviewed the available pieces of evidence supporting the direct implication of the vitamin D status in the development of osteoporosis in patients affected by inflammatory arthritis.

Furthermore, cardiovascular diseases are classical and severe complications of chronic inflammatory disorders, widely accounting for the increased mortality observed in these conditions. The atherogenic profile related to the chronic inflammatory state largely contributes to the increased cardiovascular risk; nevertheless, as broadly discussed by Bellan and Marzullo [30Bellan M, Marzullo P. New insights on low vitamin D plasma concentration as a potential cardiovascular risk factor. The Open Rheumatol J 2018; 12: 279-88.] in their manuscript here enclosed, vitamin D seems to play a critical role in the regulation of the glucose metabolism, which is a primary determinant of the cardiovascular risk. If this link is generally valid in patients affected by Type 2 Diabetes, vitamin D appears to be even more relevant in Type 1 Diabetes, in which the aberrant activity of the immune system is essential. The impact of vitamin D status on Type I Diabetes development and management has been discussed here by Savastio et al. [31Savastio S, Cadario F, Beux S, et al. Vitamin D and type I diabetes. The Open Rheumatol J 2018; 12: 289-99.]. Finally, original data about the influence of the antiviral treatment on the vitamin D/parathyroid hormone axis in chronic hepatitis C have been here presented in the manuscript by Salmi et al. [32Salmi L, Barbaglia MN, Bianco S, Guaschino G, Minisini R, Pirisi M. Detrimental impact of interferon-based regimens on vitamin D/parathyroid hormone homeostasis. The Open Rheumatol J 2018; 12: 300-12.].

REFERENCES

[1] Gil Á, Plaza-Diaz J, Mesa MD. Vitamin D: Classic and novel actions. Ann Nutr Metab 2018; 72(2): 87-95.[http://dx.doi.org/10.1159/000486536] [PMID: 29346788]
[2] Bikle DD. Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin Nephrol Hypertens 2008; 17(4): 348-52.[http://dx.doi.org/10.1097/MNH.0b013e3282ff64a3] [PMID: 18660668]
[3] Xu H, Soruri A, Gieseler RKH, Peters JH. 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes. Scand J Immunol 1993; 38(6): 535-40.[http://dx.doi.org/10.1111/j.1365-3083.1993.tb03237.x] [PMID: 8256111]
[4] Zhang Y, Leung DY, Richers BN, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 2012; 188(5): 2127-35.[http://dx.doi.org/10.4049/jimmunol.1102412] [PMID: 22301548]
[5] Piemonti L, Monti P, Sironi M, et al. Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 2000; 164(9): 4443-51.[http://dx.doi.org/10.4049/jimmunol.164.9.4443] [PMID: 10779743]
[6] Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun 2000; 270(3): 701-8.[http://dx.doi.org/10.1006/bbrc.2000.2490] [PMID: 10772887]
[7] Gauzzi MC, Purificato C, Donato K, et al. Suppressive effect of 1alpha,25-dihydroxyvitamin D3 on type I IFN-mediated monocyte differentiation into dendritic cells: Impairment of functional activities and chemotaxis. J Immunol 2005; 174(1): 270-6.[http://dx.doi.org/10.4049/jimmunol.174.1.270] [PMID: 15611249]
[8] Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007; 179(3): 1634-47.[http://dx.doi.org/10.4049/jimmunol.179.3.1634] [PMID: 17641030]
[9] Cippitelli M, Fionda C, Di Bona D, et al. Negative regulation of CD95 ligand gene expression by vitamin D3 in T lymphocytes. J Immunol 2002; 168(3): 1154-66.[http://dx.doi.org/10.4049/jimmunol.168.3.1154] [PMID: 11801650]
[10] Sloka S, Silva C, Wang J, Yong VW. Predominance of Th2 polarization by vitamin D through a STAT6-dependent mechanism. J Neuroinflammation 2011; 8: 56.[http://dx.doi.org/10.1186/1742-2094-8-56] [PMID: 21605467]
[11] Fasching P, Stradner M, Graninger W, Dejaco C, Fessler J. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules 2017; 22(1): E134.[http://dx.doi.org/10.3390/molecules22010134] [PMID: 28098832]
[12] Zhang H, Shih DQ, Zhang X. Mechanisms underlying effects of 1,25-Dihydroxyvitamin D3 on the Th17 cells. Eur J Microbiol Immunol (Bp) 2013; 3(4): 237-40.[http://dx.doi.org/10.1556/EuJMI.3.2013.4.1] [PMID: 24294492]
[13] Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis: Results from the Iowa Women’s Health Study. Arthritis Rheum 2004; 50(1): 72-7.[http://dx.doi.org/10.1002/art.11434] [PMID: 14730601]
[14] Sainaghi PP, Bellan M, Nerviani A, et al. Superiority of a high loading dose of cholecalciferol to correct hypovitaminosis d in patients with inflammatory/autoimmune rheumatic diseases. J Rheumatol 2013; 40(2): 166-72.[http://dx.doi.org/10.3899/jrheum.120536] [PMID: 23242183]
[15] Sainaghi PP, Bellan M, Carda S, et al. Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases. Rheumatol Int 2012; 32(11): 3365-72.[http://dx.doi.org/10.1007/s00296-011-2170-x] [PMID: 22045518]
[16] Sainaghi PP, Bellan M, Antonini G, Bellomo G, Pirisi M. Unsuppressed parathyroid hormone in patients with autoimmune/inflammatory rheumatic diseases: implications for vitamin D supplementation. Rheumatology (Oxford) 2011; 50(12): 2290-6.[http://dx.doi.org/10.1093/rheumatology/ker314] [PMID: 22019806]
[17] Pierrot-Deseilligny C, Souberbielle JC. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain 2010; 133(Pt 7): 1869-88.[http://dx.doi.org/10.1093/brain/awq147] [PMID: 20584945]
[18] Smolders J, Hupperts R, Barkhof F, et al. Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon β-1a: A Phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci 2011; 311(1-2): 44-9.[http://dx.doi.org/10.1016/j.jns.2011.04.013] [PMID: 21620416]
[19] Buondonno I, Rovera G, Sassi F, et al. Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study. PLoS One 2017; 12(6): e0178463.[http://dx.doi.org/10.1371/journal.pone.0178463] [PMID: 28582403]
[20] Bellan M, Sainaghi PP, Pirisi M. Role of Vitamin D in Rheumatoid Arthritis. Adv Exp Med Biol 2017; 996: 155-68.[http://dx.doi.org/10.1007/978-3-319-56017-5_13] [PMID: 29124698]
[21] Bellan M, Pirisi M, Sainaghi PP. [Osteoporosis in Rheumatoid Arthritis: Role of the vitamin D/parathyroid hormone system]. Rev Bras Reumatol 2015; 55(3): 256-63.[http://dx.doi.org/10.1016/j.rbr.2014.10.007] [PMID: 25582993]
[22] Chandrashekara S, Patted A. Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study. Int J Rheum Dis 2017; 20(7): 825-31.[http://dx.doi.org/10.1111/1756-185X.12770] [PMID: 26481198]
[23] Glade MJ. Vitamin D: Health panacea or false prophet? Nutrition 2013; 29(1): 37-41.[http://dx.doi.org/10.1016/j.nut.2012.05.010] [PMID: 23085014]
[24] Cianferotti L, Bertoldo F, Bischoff-Ferrari HA, et al. Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: Research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO). Endocrine 2017; 56(2): 245-61.[http://dx.doi.org/10.1007/s12020-017-1290-9] [PMID: 28390010]
[25] Trombetta AC, Paolino S, Cutolo M. Vitamin d, inflammation and immunity: Review of literature and considerations on recent translational and clinical research developments The Open Rheumatol J 2018; 12: 201-13.
[26] Nerviani A, Mauro D, Gilio M, Grembiale RD, Lewis M. To supplement or not to supplement? The rationale of vitamin D supplementation in systemic lupus erythematosus. The Open Rheumatol J 2018; 12: 214-25.
[27] Gualtierotti R, Di Giacomo A, Raschi E, Borghi MO, Meroni PL. Vitamin D and anti-phospholipid antibody syndrome. The Open Rheumatol J 2018; 12: 226-47.
[28] Crotti C, Becciolini A, Biggioggero M, Favalli EG. Vitamin D and spondyloarthritis: Review of the literature. The Open Rheumatol J 2018; 12: 248-60.
[29] Sainaghi PP, Gibbin A. Vitamin D, inflammation and Osteoporosis in Rheumatoid Arthritis. The Open Rheumatol J 2018; 12: 261-78.
[30] Bellan M, Marzullo P. New insights on low vitamin D plasma concentration as a potential cardiovascular risk factor. The Open Rheumatol J 2018; 12: 279-88.
[31] Savastio S, Cadario F, Beux S, et al. Vitamin D and type I diabetes. The Open Rheumatol J 2018; 12: 289-99.
[32] Salmi L, Barbaglia MN, Bianco S, Guaschino G, Minisini R, Pirisi M. Detrimental impact of interferon-based regimens on vitamin D/parathyroid hormone homeostasis. The Open Rheumatol J 2018; 12: 300-12.

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


SCImago Journal Ranking

SCImago Journal & Country Rank

Browse Contents



Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open