Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial

Critical Care Medicine

Volumn 43, Issue 9, 2015, Pages 1928-1937

  Quraishi, Sadeq A ^a,b   De Pascale, Gennaro ^a,b   Needleman, Joseph S ^b   Nakazawa, Harumasa ^b   Kaneki, Masao ^a,b,c   Bajwa, Ednan K ^a,b   Camargo, Carlos A ^a,b,d   Bhan, Ishir ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c SHRINERS HOSPITALS FOR CHILDREN   (United States)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

25 hydroxyvitamin; cathelicidin; cholecalciferol; intensive care unit; LL 37; Vitamin D

Indexed keywords

25 HYDROXYVITAMIN D; ALBUMIN; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; COLECALCIFEROL; PLACEBO; VITAMIN D BINDING PROTEIN; 25-HYDROXYVITAMIN D; ANTIMICROBIAL CATIONIC PEPTIDE; CALCIFEDIOL; CAP18 LIPOPOLYSACCHARIDE-BINDING PROTEIN; SERUM ALBUMIN; VITAMIN D;

ADULT; AGED; ARTICLE; BIOAVAILABILITY; BLOOD SAMPLING; CONTROLLED STUDY; CRITICALLY ILL PATIENT; DRUG EFFICACY; FEMALE; HUMAN; INTENSIVE CARE UNIT; KRUSKAL WALLIS TEST; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; SEPSIS; SEPTIC SHOCK; VITAMIN BLOOD LEVEL; VITAMIN SUPPLEMENTATION; ANALOGS AND DERIVATIVES; BLOOD; DIET SUPPLEMENTATION; MIDDLE AGED; TEACHING HOSPITAL;

ADULT; ANTIMICROBIAL CATIONIC PEPTIDES; BIOMARKERS; C-REACTIVE PROTEIN; CALCIFEDIOL; CHOLECALCIFEROL; DIETARY SUPPLEMENTS; FEMALE; HOSPITALS, TEACHING; HUMANS; INTENSIVE CARE UNITS; MALE; MIDDLE AGED; SEPSIS; SERUM ALBUMIN; SHOCK, SEPTIC; VITAMIN D;

EID: 84942117832     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0000000000001148     Document Type: Article

References (75)

1. Bone RC, Balk RA, Cerra FB, et al: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Micine. Chest 1992; 101:1644-1655
2. Levy MM, Fink MP, Marshall JC, et al; SCCM/ESICM/ACCP/ATS/SIS: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care M 2003; 31:1250-1256
3. Danai P, Martin GS: Epidemiology of sepsis: Recent advances. Curr Infect Dis Rep 2005; 7:329-334
4. Gaieski DF, wards JM, Kallan MJ, et al: The relationship between hospital volume and mortality in severe sepsis. Am J Respir Crit Care M 2014; 190:665-674
5. Stevenson EK, Rubenstein AR, Radin GT, et al: Two decades of mortality trends among patients with severe sepsis: A comparative metaanalysis. Crit Care M 2014; 42:625-631
6. Kaukonen KM, Bailey M, Suzuki S, et al: Mortality relat to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA 2014; 311:1308-1316
7. Gaieski DF, wards JM, Kallan MJ, et al: Benchmarking the incidence and mortality of severe sepsis in the Unit States. Crit Care M 2013; 41:1167-1174
8. Martin GS, Mannino DM, Eaton S, et al: The epidemiology of sepsis in the Unit States from 1979 through 2000. N Engl J M 2003; 348:1546-1554
9. Dombrovskiy VY, Martin AA, Sunderram J, et al: Rapid increase in hospitalization and mortality rates for severe sepsis in the Unit States: A trend analysis from 1993 to 2003. Crit Care M 2007; 35:1244-1250
10. Lagu T, Rothberg MB, Shieh MS, et al: Hospitalizations, costs, and outcomes of severe sepsis in the Unit States 2003 to 2007. Crit Care M 2012; 40:754-761
11. Elixhauser A, Friman B, Stranges E: Septicemia in U.S. Hospitals, 2009: Statistical Brief #122. Rockville, MD, Agency for Healthcare Research and Quality. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf. Access May 15, 2013
12. Esper AM, Martin GS: Extending international sepsis epidemiology: The impact of organ dysfunction. Crit Care 2009; 13:120
13. Blanco J, Muriel-Bombín A, Sagro V, et al; Grupo de Estudios y Análisis en Cuidados Intensivos: Incidence, organ dysfunction and mortality in severe sepsis: A Spanish multicentre study. Crit Care 2008; 12:R158
14. Adams JS, Hewison M: Unexpect actions of vitamin D: New perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab 2008; 4:80-90
15. Fabri M, Stenger S, Shin DM, et al: Vitamin D is requir for IFNgamma-miat antimicrobial activity of human macrophages. Sci Transl M 2011; 3:104ra102
16. Kankova M, Luini W, Prazzoni M, et al: Impairment of cytokine production in mice f a vitamin D3-deficient diet. Immunology 1991; 73:466-471
17. Quraishi SA, Camargo CA Jr: Vitamin D and chronic illness. J Restor M 2012; 1:9-23
18. Holick MF: Evidence-bas D-bate on health benefits of vitamin D revisit. Dermatoendocrinol 2012; 4:183-190
19. Lucidarme O, Messai E, Mazzoni T, et al: Incidence and risk factors of vitamin D deficiency in critically ill patients: Results from a prospective observational study. Intensive Care M 2010; 36:1609-1611
20. Lee P, Eisman JA, Center JR: Vitamin D deficiency in critically ill patients. N Engl J M 2009; 360:1912-1914
21. Venkatram S, Chilimuri S, Adrish M, et al: Vitamin D deficiency is associat with mortality in the mical intensive care unit. Crit Care 2011; 15:R292
22. Braun A, Chang D, Mahadevappa K, et al: Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care M 2011; 39:671-677
23. Braun AB, Gibbons FK, Litonjua AA, et al: Low serum 25-hydroxyvitamin D at critical care initiation is associat with increas mortality. Crit Care M 2012; 40:63-72
24. Cecchi A, Bonizzoli M, Douar S, et al: Vitamin D deficiency in septic patients at ICU admission is not a mortality prictor. Minerva Anestesiol 2011; 77:1184-1189
25. Kempker JA, Han JE, Tangpricha V, et al: Vitamin D and sepsis: An emerging relationship. Dermatoendocrinol 2012; 4:101-108
26. Jeng L, Yamshchikov AV, Judd SE, et al: Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl M 2009; 7:28
27. Ginde AA, Camargo CA Jr, Shapiro NI: Vitamin D insufficiency and sepsis severity in emergency department patients with suspect infection. Acad Emerg M 2011; 18:551-554
28. Pinheiro da Silva F, Machado MC: Antimicrobial peptides: Clinical relevance and therapeutic implications. Peptides 2012; 36:308-314
29. Dellinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis Campaign Guidelines Committee including the Piatric Subgroup: Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care M 2013; 41:580-637
30. Gusmao-Flores D, Salluh JI, Chalhub RÁ, et al: The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: A systematic review and meta-analysis of clinical studies. Crit Care 2012; 16:R115
31. Quraishi SA, Bittner EA, Blum L, et al: Prospective study of vitamin D status at initiation of care in critically ill surgical patients and risk of 90-day mortality. Crit Care M 2014; 42:1365-1371
32. Amrein K, Sourij H, Wagner G, et al: Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: A randomiz, double-blind, placebo-controll pilot study. Crit Care 2011; 15:R104
33. Liu PT, Stenger S, Tang DH, et al: Cutting ge: Vitamin D-miat human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol 2007; 179:2060-2063
34. Liu PT, Stenger S, Li H, et al: Toll-like receptor triggering of a vitamin D-miat human antimicrobial response. Science 2006; 311:1770-1773
35. Bhalla AK, Amento EP, Krane SM: Differential effects of 1,25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: Inhibition of interleukin-2 and augmentation of interleukin-1 production. Cell Immunol 1986; 98:311-322
36. Dürr UH, Sudheendra US, Ramamoorthy A: LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 2006; 1758:1408-1425
37. Quraishi SA, Camargo CA Jr: Vitamin D in acute stress and critical illness. Curr Opin Clin Nutr Metab Care 2012; 15:625-634
38. Amrein K, Venkatesh B: Vitamin D and the critically ill patient. Curr Opin Clin Nutr Metab Care 2012; 15:188-193
39. Leaf DE, Waikar SS, Wolf M, et al: Dysregulat mineral metabolism in patients with acute kidney injury and risk of adverse outcomes. Clin Endocrinol (Oxf) 2013; 79:491-498
40. Prosser DE, Jones G: Enzymes involv in the activation and inactivation of vitamin D. Trends Biochem Sci 2004; 29:664-673
41. Bhan I, Powe CE, Berg AH, et al: Bioavailable vitamin D is more tightly link to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 2012; 82:84-89
42. De Pascale G, Quraishi SA: Vitamin D status in critically ill patients: The evidence is now bioavailable! Crit Care 2014; 18:449
43. Zanetti M, Gennaro R, Romeo D: Cathelicidins: A novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett 1995; 374:1-5
44. Scocchi M, Skerlavaj B, Romeo D, et al: Proteolytic cleavage by neutrophil elastase converts inactive storage proforms to antibacterial bactenecins. Eur J Biochem 1992; 209:589-595
45. Larrick JW, Hirata M, Balint RF, et al: Human CAP18: A novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 1995; 63:1291-1297
46. Sørensen O, Arnljots K, Cowland JB, et al: The human antibacterial cathelicidin, hCAP-18, is synthesiz in myelocytes and metamyelocytes and localiz to specific granules in neutrophils. Blood 1997; 90:2796-2803
47. Agerberth B, Charo J, Werr J, et al: The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are express by specific lymphocyte and monocyte populations. Blood 2000; 96:3086-3093
48. Frohm Nilsson M, Sandstt B, Sørensen O, et al: The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely express in human squamous epithelia and colocalizes with interleukin-6. Infect Immun 1999; 67:2561-2566
49. Bals R, Wang X, Zasloff M, et al: The peptide antibiotic LL-37/hCAP-18 is express in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA 1998; 95:9541-9546
50. Frohm M, Agerberth B, Ahangari G, et al: The expression of the gene coding for the antibacterial peptide LL-37 is induc in human keratinocytes during inflammatory disorders. J Biol Chem 1997; 272:15258-15263
51. Sørensen O, Bratt T, Johnsen AH, et al: The human antibacterial cathelicidin, hCAP-18, is bound to lipoproteins in plasma. J Biol Chem 1999; 274:22445-22451
52. Turner J, Cho Y, Dinh NN, et al: Activities of LL-37, a cathelin-associat antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 1998; 42:2206-2214
53. Nagaoka I, Hirota S, Yomogida S, et al: Synergistic actions of antibacterial neutrophil defensins and cathelicidins. Inflamm Res 2000; 49:73-79
54. De Yang, Chen Q, Schmidt AP, et al: LL-37, the neutrophil granule-and epithelial cell-deriv cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp M 2000; 192:1069-1074
55. Tollin M, Bergman P, Svenberg T, et al: Antimicrobial peptides in the first line defence of human colon mucosa. Peptides 2003; 24:523-530
56. Parameswaran N, Patial S: Tumor necrosis factor-? signaling in macrophages. Crit Rev Eukaryot Gene Expr 2010; 20:87-103
57. Schouten M, Wiersinga WJ, Levi M, et al: Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol 2008; 83:536-545
58. Pittet D, Rangel-Frausto S, Li N, et al: Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: Incidence, morbidities and outcomes in surgical ICU patients. Intensive Care M 1995; 21:302-309
59. Fong Y, Tracey KJ, Moldawer LL, et al: Antibodies to cachectin/tumor necrosis factor ruce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp M 1989; 170:1627-1633
60. Surbatovic M, Veljovic M, Jevdjic J, et al: Immunoinflammatory response in critically ill patients: Severe sepsis and/or trauma. Miators Inflamm 2013; 2013:362793
61. Chai Z, Gatti S, Toniatti C, et al: Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: A study on IL-6-deficient mice. J Exp M 1996; 183:311-316
62. Kopf M, Baumann H, Freer G, et al: Impair immune and acutephase responses in interleukin-6-deficient mice. Nature 1994; 368:339-342
63. Tilg H, Dinarello CA, Mier JW: IL-6 and APPs: Anti-inflammatory and immunosuppressive miators. Immunol Today 1997; 18:428-432
64. Pathan N, Hemingway CA, Alizadeh AA, et al: Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet 2004; 363:203-209
65. Okamura H, Kashiwamura S, Tsutsui H, et al: Regulation of interferongamma production by IL-12 and IL-18. Curr Opin Immunol 1998; 10:259-264
66. Calandra T, Baumgartner JD, Grau GE, et al: Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis 1990; 161:982-987
67. Flohé SB, Agrawal H, Flohé S, et al: Diversity of interferon gamma and granulocyte-macrophage colony-stimulating factor in restoring immune dysfunction of dendritic cells and macrophages during polymicrobial sepsis. Mol M 2008; 14:247-256
68. Leentjens J, Kox M, Koch RM, et al: Reversal of immunoparalysis in humans in vivo: A double-blind, placebo-controll, randomiz pilot study. Am J Respir Crit Care M 2012; 186:838-845
69. de Waal Malefyt R, Abrams J, Bennett B, et al: Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produc by monocytes. J Exp M 1991; 174:1209-1220
70. Fiorentino DF, Zlotnik A, Mosmann TR, et al: IL-10 inhibits cytokine production by activat macrophages. J Immunol 1991; 147:3815-3822
71. Latifi SQ, O'Riordan MA, Levine AD: Interleukin-10 controls the onset of irreversible septic shock. Infect Immun 2002; 70:4441-4446
72. Manley MO, O'Riordan MA, Levine AD, et al: Interleukin 10 extends the effectiveness of standard therapy during late sepsis with serum interleukin 6 levels pricting outcome. Shock 2005; 23:521-526
73. Leaf DE, Ra A, Donnino MW, et al: Randomiz controll trial of calcitriol in severe sepsis. Am J Respir Crit Care M 2014; 190:533-541
74. Amrein K, Schnl C, Holl A, et al: Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: The VITdAL-ICU randomiz clinical trial. JAMA 2014; 312:1520-1530
75. Rousseau AF, Damas P, Janssens M, et al: Critical care and vitamin D status assessment: What about immunoassays and calculat free 25OH-D? Clin Chim Acta 2014; 437:43-47