The effect of vitamin D on different human cells, with emphasis on burns and ICU – April 2018

Vitamin D status and its influence on outcomes following major burn injury and critical illness

Burns & Trauma 20186:11, https://doi.org/10.1186/s41038-018-0113-4, 16 April 2018
Khaled Al-Tarrah, Martin Hewison, Naiem Moiemen† and Janet M. Lord† † = Contributed equally

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Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients. Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the clinical implications and consequences of vitamin D deficiency in acute contexts remain to be fully understood. Vitamin D has a broad range of pleotropic effects on various processes and systems including the immune-inflammatory response. 1α,25-dihydroxyvitamin D (1,25(OH)2D), has been shown to promote a tolerogenic immune response limiting deleterious inflammatory effects, modulation of the innate immune system, and enhancement of anti-microbial peptides. Vitamin D deficiency is frequently observed in critically ill patients and has been related to extrinsic causes (i.e., limited sunlight exposure), magnitude of injury/illness, or the treatment started by medical doctors including fluid resuscitation. Low levels of vitamin D in critically ill patients have been associated with sepsis, organ failure, and mortality. Despite this, there are subpopulations of critical illness, such as burn patients, where the literature regarding vitamin D status and its influence on outcomes remain insufficient. Thermal injury results in damage to both burned and non-burned tissues, as well as induces an exaggerated and persistent immune-inflammatory and hypermetabolic response. In this review, we propose potential mechanisms in which burn injury affects the vitamin D status and summarizes current literature investigating the influence of vitamin D status on outcomes. In addition, we reviewed the literature and trials investigating vitamin D supplementation in critically ill patients and discuss the therapeutic potential of vitamin D supplementation in burn and critically ill patients. We also highlight current limitations of studies that have investigated vitamin D status and supplementation in critical illness. Thermal injury influences vitamin D status. More studies investigating vitamin D depletion in burn patients and its influence on prognosis, via standardized methodology, are required to reach definitive conclusions and influence clinical practice.

Table 1 Effects of vitamin D on various human cell types and tissues

Adipocytes [105]
Inhibits intracellular fat accumulation
Enhances basallipolysis without cell toxicity
Upregulation of p-oxidation-related genes, lipolytic enzymes, and vitamin D-responsive genes
Increased levels of nicotinamide adenine dinucleotide and sirtulin 1 expression

Cardiomyocytes[106, 107]
Inhibition of cellproliferation without apoptosis
Downregulation of expression of genes associated with cell cycle regulation
Promotes cardiomyotube formation
Induces cardiac differentiation

Hepatocytes[108-110]
Protects against insulin resistance
Downregulates fibrogenic TGF-p signaling
Anti-inflammatory effects by inhibiting monocyte activation and TNF-a and IL-1 expression

Myocytes [111,112]
Modulation of calcium homeostasis and influx
Induces cellular proliferation and differentiation
Protects against insulin resistance
Stimulation of arachidonic acid mobilization

Nephrocytes [113]
Upregulation of cellular metabolic activity, IL-6, and reactive oxygen species
Restoration of transepithelial barrier function

Neurons  [114, 115]
Neuroactive steroid modulating spontaneous regular firing, actin potential duration, and intrinsic excitability
Enhances sensitivity to neurotransmitters and neurotransmitter receptors
Upregulation of neuronal growth factors, neurotrophin 3, and glial cell line-derived neurotrophic factor

T cells[17, 116]
Inhibits Th1/Th17 chemokine/ cytokine secretion (CXCL-10, IFN-γ, TNF-α, and IL-17)
Enhances Th2 cytokine release (IL-4 and IL-5)

B cells [117]
Downregulates the proliferation of memory B cells
Inhibits plasma cell differentiation
Reduces Ig production

Antigenpresenting cells[122]
Inhibits the expression of class II MHC molecules (HLA-DR)
Inhibition of co-stimulating molecule expression (CD80, CD83, and CD86)
Augments chemotaxis and phagocytosis of monocytes
Downregulates the maturation of dendritic cells
Induces tolerogenic dendritic cells capable of inducing Treg cells
Inhibits IL-12 p70 release
Decreases macrophagestimulated pro-inflammatory cytokine production (IL-1, IL-1β, IL-6, IL-8, MCP-1, and RANTES)

NK cells[122]
Inhibition of NK cell development and differentiation
Reduced INF-γ and cytotoxicity