title: Vitamin D Deficiency in Human and Murine Sepsis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: 1Centre for Translational Inflammation Research, Institute of Inflammation and Aging, University of Birmingham, Birmingham, United Kingdom. 2Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom. 3Academic Department of Anesthesia, Critical Care, Resuscitation and Pain, Heart of England NHS Foundation Trust, Bordesley Green, Birmingham, United Kingdom. 4Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Parekh
authors.forename: Jaimin M
authors.initials: JM
authors.lastname: Patel
authors.forename: Aaron
authors.initials: A
authors.lastname: Scott
authors.forename: Sian
authors.initials: S
authors.lastname: Lax
authors.forename: Rachel C A
authors.initials: RC
authors.lastname: Dancer
authors.forename: Vijay
authors.initials: V
authors.lastname: D'Souza
authors.forename: Hannah
authors.initials: H
authors.lastname: Greenwood
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sapey
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett
mesh_terms: D000368:Aged; D000818:Animals; D002112:Calcifediol / Q000097:blood; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012307:Risk Factors; D018805:Sepsis / Q000209:etiology* / Q000401:mortality; D014808:Vitamin D Deficiency / Q000150:complications*
chemical_list: D002112:Calcifediol