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Vitamin D deficiency in human and murine sepsis
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Parekh, Dhruv, Patel, Jaimin M., Scott, Aaron, Lax, Sian, Dancer, Rachel C. A., D’Souza, Vijay, Greenwood, Hannah, Fraser, William D., Gao Smith, Fang, Sapey, Elizabeth, Perkins, Gavin D. and Thickett, David R. (2017) Vitamin D deficiency in human and murine sepsis. Critical Care Medicine, 45 (2). pp. 282-289. doi:10.1097/CCM.0000000000002095
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WRAP-Vitamin-D-Deficiency-Human-Murine-Perkins-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1083Kb) | Preview |
Official URL: http://dx.doi.org/10.1097/CCM.0000000000002095
Abstract
OBJECTIVES
Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and ICU mortality but causality of these associations has not been demonstrated. To determine whether sepsis and severe sepsis are associated with vitamin D deficiency and to determine whether vitamin D deficiency influences the severity of sepsis.
DESIGN, SETTING, AND PATIENTS
Sixty-one patients with sepsis and severe sepsis from two large U.K. hospitals and 20 healthy controls were recruited. Murine models of cecal ligation and puncture and intratracheal lipopolysaccharide were undertaken in normal and vitamin D deficient mice to address the issue of causality.
MEASUREMENTS AND MAIN RESULTS
Patients with severe sepsis had significantly lower concentrations of 25-hydroxyvitamin D3 than patients with either mild sepsis or age-matched healthy controls (15.7 vs 49.5 vs 66.5 nmol/L; p = 0.0001). 25-hydroxyvitamin D3 concentrations were significantly lower in patients who had positive microbiologic culture than those who were culture negative (p = 0.0023) as well as those who died within 30 days of hospital admission (p = 0.025). Vitamin D deficiency in murine sepsis was associated with increased peritoneal (p = 0.037), systemic (p = 0.019), and bronchoalveolar lavage (p = 0.011) quantitative bacterial culture. This was associated with reduced local expression of the cathelicidin-related antimicrobial peptide as well as evidence of defective macrophage phagocytosis (p = 0.029). In the intratracheal lipopolysaccharide model, 1,500 IU of intraperitoneal cholecalciferol treatment 6 hours postinjury reduced alveolar inflammation, cellular damage, and hypoxia.
CONCLUSIONS
Vitamin D deficiency is common in severe sepsis. This appears to contribute to the development of the condition in clinically relevant murine models and approaches to correct vitamin D deficiency in patients with sepsis should be developed.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology | ||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Vitamin D deficiency., Vitamin D in human nutrition., Septicemia., Blood -- Diseases. | ||||||
| Journal or Publication Title: | Critical Care Medicine | ||||||
| Publisher: | Lippincott Williams & Wilkins | ||||||
| ISSN: | 0090-3493 | ||||||
| Official Date: | 1 February 2017 | ||||||
| Dates: |
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| Date of first compliant deposit: | 20 April 2017 | ||||||
| Volume: | 45 | ||||||
| Number: | 2 | ||||||
| Page Range: | pp. 282-289 | ||||||
| DOI: | 10.1097/CCM.0000000000002095 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access |
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