The role of vitamin D deficiency in sepsis and potential therapeutic implications

Division of Infectious Diseases, Akron General Medical Center, Akron, OH 44302, USA.
The Journal of infection (Impact Factor: 4.44). 07/2011; 63(5):321-6. DOI: 10.1016/j.jinf.2011.07.002
Source: PubMed


Recent studies have shown that vitamin D has important functions besides bone and calcium homeostasis. Cells of the innate and adaptive immune system express vitamin D receptors and respond to stimulation by 1, 25-dihydroxyvitamin D. Patients with sepsis have a high mortality rate as well as a high prevalence of vitamin D deficiency. In addition, septic patients have decreased vitamin D binding protein levels which further exacerbates vitamin D deficiency. Therapy with vitamin D in animal models of sepsis improves blood coagulation parameters in disseminated intravascular coagulation and modulates levels of systemic inflammatory cytokines including TNF-α and IL-6. Vitamin D can enhance the induction of the antimicrobial peptides cathelicidin and β-defensin which are found on mucosal and epithelial surfaces and act as the body's first line of defense against viral and bacterial pathogens. Vitamin D is potentially an attractive therapeutic agent for sepsis given its low cost and low risk of toxicity and side effects. Further prospective, randomized, controlled clinical trials of adjunctive vitamin D therapy in patients who are deficient are needed in the management of human sepsis syndrome.

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    • "Patients with sepsis have a high mortality rate as well as a high prevalence of vitamin D deficiency. In addition, septic patients have decreased DBP levels, which further exacerbate the total low vitamin D levels but might attenuate the risk of vitamin D deficiency by maintaining normal free or bioavailable 25(OH)D [50]. Jeng et al. found that 25(OH)D and DBP levels were lower in patients in the intensive care unit with sepsis compared with healthy controls [51]. "
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    ABSTRACT: There is a high prevalence of vitamin D deficiency worldwide, but how to define vitamin D deficiency is controversial. Currently, the plasma concentration of total 25-hydroxyvitamin D [25(OH)D] is considered an indicator of vitamin D status. The free hormone hypothesis states that protein-bound hormones are inactive while unbound hormones are free to exert biological activity. The majority of circulating 25(OH)D and 1,25(OH)2D is tightly bound to vitamin D binding protein (DBP), 10-15% is bound to albumin, and less than 1% of circulating vitamin D exists in an unbound form. While DBP is relatively stable in most healthy populations, a recent study showed that there are gene polymorphisms associated with race and ethnicity that could alter DBP levels and binding affinity. Furthermore, in some clinical situations, total vitamin D levels are altered and knowing whether DBP is also altered may have treatment implications. The aim of this review is to assess DBP concentration in different physiological and pathophysiological conditions. We suggest that DBP should be considered in the interpretation of 25(OH)D levels.
    International Journal of Endocrinology 04/2014; 2014(3):981581. DOI:10.1155/2014/981581 · 1.95 Impact Factor
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    • "Vitamin D-binding protein levels in plasma were significantly lower in critically ill subjects with sepsis than in critically ill subjects without sepsis.47 Therapy with vitamin D in animal models of sepsis improves blood coagulation parameters in disseminated intravascular coagulation and modulates levels of systemic inflammatory cytokines, including tumor necrosis factor α and interleukin 6.48 "
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    ABSTRACT: Health care–associated and hospital-acquired infections are two entities associated with increased morbidity and mortality. They are highly costly and constitute a great burden to the health care system. Vitamin D deficiency (< 20 ng/ml) is prevalent and may be a key contributor to both acute and chronic ill health. Vitamin D deficiency is associated with decreased innate immunity and increased risk for infections. Vitamin D can positively influence a wide variety of microbial infections. Herein we discuss hospital-acquired infections, such as pneumonia, bacteremias, urinary tract and surgical site infections, and the potential role vitamin D may play in ameliorating them. We also discuss how vitamin D might positively influence these infections and help contain health care costs. Pending further studies, we think it is prudent to check vitamin D status at hospital admission and to take immediate steps to address existing insufficient 25-hydroxyvitamin D levels.
    Dermato-Endocrinology 04/2012; 4(2):167-75. DOI:10.4161/derm.20789
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    ABSTRACT: Vitamin D(3) deficiency is a highly prevalent condition worldwide. Clinically, vitamin D(3) has a key role in calcium homeostasis and bone mineralization and has recently been implicated in the pathogenesis and/or progression of several acute and chronic illnesses, including cardiovascular disease (CVD). Accumulating evidence from observational, prospective studies suggests that low levels of serum 25-hydroxyvitamin D(3) are independently associated with an increased risk of CVD events and death. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a cardiovascular role for the active metabolite of vitamin D(3). 1-α,25-dihydroxyvitamin D(3) regulates the renin-angiotensin system, suppresses proliferation of vascular cell smooth muscle, improves insulin resistance and endothelial cell-dependent vasodilation, inhibits myocardial cell hypertrophy, exerts anticoagulant and antifibrotic activity, and modulates macrophage activity and cytokine generation. Overall, the high prevalence of vitamin D(3) deficiency and the plausible biological mechanisms linking this to CVD risk suggest that the treatment of vitamin D(3) deficiency to prevent CVD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D supplementation could have any potential benefit in reducing future CVD events and mortality risk.
    Seminars in Thrombosis and Hemostasis 02/2012; 38(1):114-24. DOI:10.1055/s-0031-1300957 · 3.88 Impact Factor
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