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Vitamin D Deficiency in Human and Murine Sepsis.

Parekh, Dhruv and Patel, Jaimin M and Scott, Aaron and Lax, Sian and Dancer, Rachel C A and D'Souza, Vijay and Greenwood, Hannah and Fraser, William D and Gao, Fang and Sapey, Elizabeth and Perkins, Gavin D and Thickett, David R (2017) Vitamin D Deficiency in Human and Murine Sepsis. Critical care medicine, 45 (2). pp. 282-289. ISSN 1530-0293. This article is available to all HEFT staff and students via ASK HEFT Discovery tool http://tinyurl.com/z795c8c using their HEFT Athens Login.

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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: Article
Additional Information: This article is available to all HEFT staff and students via ASK HEFT Discovery tool http://tinyurl.com/z795c8c using their HEFT Athens Login.
Subjects: WC Communicabable diseases
Divisions: Clinical Support > Critical Care
Related URLs:
Depositing User: Mrs Adele Creak
Date Deposited: 03 Mar 2017 11:55
Last Modified: 03 Mar 2017 11:55
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1226

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