The value of the pleiotropic effects of vitamin D in post-shock period with severe concomitant injury

Written by Shumatov V.B., Pavlov V.A., Gorozhin P.Yu., Ermakov N.D., Lazanovich V.A.

  UDK: 617-001.36-031.81-085.37 | Pages: 9–13 | Full text PDF | Open PDF 


The review presents the role of systemic inflammation in the pathogenesis of immune suppression with serious injury. Clinically, many patients with symptoms of systemic inflammation and organ damage immunologically caused, i.e. in the phase anticipated activation of pro-inflammatory mediators are both very susceptible to secondary infections. Particularly significant features of both dual activation and suppression appear in neutrophils. Organ dysfunction in critical condition is largely caused by neutrophils. The interaction with the immune system is one of the important effects of vitamin D. The active form of vitamin D regulates the acquisition and innate immunity, as vitamin D receptors are presented in many cells of the immune system such as macrophages, dendritic cells, and T- and B-lymphocytes. Many studies confirmed that the lack of vitamin D or its receptors can cause disorders of the innate and adaptive immunity. Effect of vitamin D on the immune system may be caused by inverse connection paracrine mechanism by which an inflammatory response is reduced, and by the influence on the differentiation of T helper lymphocytes and suppression of their function. In this regard, it is extremely important to understand the epidemiology of vitamin D deficiency among the resuscitation patients to find out the value of its deficit in the formation of multiple organ dysfunction syndrome in post-shock period and prognosis in severe concomitant injury.

Links to authors:

V.B. Shumatov, V.A. Pavlov, P.Yu. Gorozhin, N.D. Ermakov, V.A. Lazanovich
Pacific State Medical University (2 Ostryakova Ave. Vladivostok 690950 Russian Federation)

1. Adibconquy M., Cavaillon J. Stress molecules in sepsis and systemic inflammatory response syndrome // FEBS Letters. 2007. Vol. 581. P. 3723–3733.
2. Arraes S.M., Freitas M.S., da Silva S.V. Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation // Blood. 2006. Vol. 108. P. 2906–2913.
3. Bianchi M.E. DAMPs, PAMPs and alarming: all we to know about danger // Journal of Leukocyte Biology. 2007. Vol. 81. P. 1–5.
4. Bone R.C. Sir Isaac Newton, sepsis, SIRS, and CARS // Critical Care Medicine. 1996. Vol. 24. P. 1125–1128.
5. Brown K.A., Brain S.D., Pearson J.D. Neutrophils in development of multiple organ failure in sepsis // Lancet. 2006. Vol. 368. P. 157–169.
6. Chastre J., Fagon J. Ventilator-associated pneumonia // American Journal of Respiratory and Critical Care Medicine. 2002. Vol. 165, No. 7. P. 856–903.
7. Danikas D.D., Karakantza M., Theodorou G.L. Prognostic value of phagocytic activity of neutrophils and monocytes in sepsis. Correlation to CD64 and CD14 antigen expression // Clinical & Experimental Immunology. 2008. Vol. 154. P. 87–97.
8. Docke W., Randow F., Sybre U. Monocyte deactivation in septic patients: restoration by INF-gamma treatment // Nature Medicine. 1997. Vol. 3. P. 678–681.
9. Ertel W., Jarrar D., Jochum M. Enhanced release of elastase is not concomitant with increased secretion of granulocyte-activating cytokines in whole blood from patients with sepsis // Archives of surgery. 1994. Vol. 129, No. 1. P. 90–97.
10. Flone S.B., Agrawal H., Rani M. Diversity of interferon gamma and granulocyte-macrophage colony-stimulating factor in restoring immune dysfunction of dendritic cells and macrophages during polymicrobial sepsis // Molecular Medicine. 2008. Vol. 14, No. 4–5. P. 247–256.
11. Fosse E., Pillgram-Larsen J., Svennevig J.L. Complement activation in injured patients occurs immediately and is dependent on the severity of the trauma // Injury. 1998. Vol. 29, No. 7. P. 509–514.
12. Gorgoni B., Maritano D., Marthyn P. [et al.] V. C/EBP beta gene inactivation causes both impaired and enhanced gene expression and inverse regulation of IL-12 p40 and p35 mRNAs in macrophages// Journal of Immunology. 2002. Vol. 168, No. 8. P. 4055–4062.
13. Grandinali M., Padalino P., Vesconi S. Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease // Archives of surgery. 1992. Vol. 127. P. 1219–1224.
14. Hayes C. E., Nashold F. E., Spach K. M. [et al.]. The immunological functions of the Vitamin D endocrine system // Cellular and Molecular Biology. 2003. Vol. 49, No. 2. P. 277–300.
15. Heidecke C.D., Hensler T., Weighardt H. Selective defects of T lymphocyte function in patients with lethal intraabdominal infection// The American Journal of Surgical Pathology. 1999. Vol. 178, No. 4. P. 288–292.
16. Hotchkiss R.S., Karl I.E. The pathophysiology and treatment of sepsis // New England Journal of Medicine. 2003. Vol. 348, No. 2. P. 138–150.
17. Huber-Lung M., Younkin E.M., Sarma J.V. Complement-induced impairment of innate immunity during sepsis // The Journal of Immunology. 2002. Vol. 169, No. 6. P. 3223–3231.
18. Hullett D. A., Cantorna M. T., Redaelli C. [et al.]. Prolongation of allograft survival by 1,25-dihydroxyVitamin D3 // Transplantation. 1998. Vol. 66, No. 7. P. 824–828.
19. Ji Y., Studzinski G. P. Retinoblastoma protein and CCAAT/ enhancer-binding protein beta are required for 1,25-dihydroxyVitamin D3-induced monocytic differentiation of HL60 cells // Cancer Research. 2004. Vol. 64, No. 1. P. 370–377.
20. Kothari N., Keshari R.S., Borga J. Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis // Journal of Critical Care. 2011. Vol. 26, No. 4. P. 435.e1–435.e7.
21. Liu M., Lee M., Cohen M. [et al.]. Transcriptional activation of the Cdk inhibitor p21 by Vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937 // Genes and Development. 1996. Vol. 10, No. 2. P. 142–153.
22. Liu N., Kaplan A. T., Low J. Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway 1 // Biology of Reproduction. 2009. Vol. 80, No. 3. P. 398–406.
23. Lukaszeicz A.C., Grienay M., Resche-Rigon M. Monocytic HLADR expression in intensive care patients: interest for prognosis and secondary infection prediction // Critical Care Medicine. 2009. Vol. 37, No. 10. P. 2746–2752.
24. Meisel C., Schefold J.C., Pschowski R. Granulocyte-macrofage colonystimulating factor to reverse sepsis-associated immunosuppression: A double blind, randomized, placebo-controlled multicenter trial // American Journal of Respiratory and Critical Care Medicine. 2009. Vol. 180, No. 7. P. 640–648.
25. Miyaoka K., Iwase M., Suzuki R. [et al.]. Clinical evaluation of circulating interleukin-6 and interleukin-10 levels after surgeryinduced inflammation // Journal of Surgical Research. 2005. Vol. 125. P. 144–150.
26. Mohr A., Polz J., Martin E.M. Sepsis leads to a reduced antigenspecific primary antibody response // European Journal of Immunology. 2012. Vol. 42, No. 2. P. 341–352.
27. Morris A.C., Kefala K., Wilkinson T.S. C5a mediates peripheral blood neutrophil dysfunction in critically ill patients // American Journal of Respiratory and Critical Care Medicine. 2009. Vol. 180. P. 19–28.
28. Morris A.C., Kefala K., Wilkinson T.S. C5a-mediated neutrophil phagocytic dysfunction is RhoA-dependent and predicts nosocomial infection in critically ill patients // Blood. 2011. Vol. 117, No. 19. P. 5178–5188.
29. Morris A.C., Kefala K., Wilkinson T.S. Diagnostic importance of pulmonary interleukin-1 beta and interleukin-8 in ventilator-associated pneumonia // Thorax. 2010. Vol. 65, No. 3. P. 201–207.
30. Muller Kobold A., Tulleken J.E., Zijlstra J.G. Leukocyte activation in sepsis; correlation with disease state and mortality // Intensive Care Medicine. 2000. Vol. 26, No. 7. P. 883–892.
31. Nizet V., Ohtake T., Lauth X. Innate antimicrobial peptide protects the skin from invasive bacterial infection // Nature. 2001. Vol. 414, No. 6862. P. 454–457.
32. Nuijens J.H., Abbink J.J., Wachtfogel Y.T. Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis // Journal of Laboratory and Clinical Medicine. 1992. Vol. 119. P. 159–168.
33. Oppermann M., Gotze O. Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors // Immunology. 1994. Vol. 82, No. 4. P. 516–521.
34. Osuchowski M.F., Welch K., Siddiqui J. Circulating cytokine/ inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality // Journal of Immunology. 2006. Vol. 177, No. 3. P. 1967–1974.
35. Pellizzer G., Mantoan P., Timillero L. [et al.]. Prevalence and risk factors for nosocomial infections in hospitals of the Veneto region, north-eastern Italy // Infection. 2008. Vol. 36, No. 2. P. 112–119.
36. Rittirsch D., Flierl M., Ward P. Harmful molecular mechanisms in sepsis // Nature Reviews Immunology. 2008. Vol. 8. P. 776–787.
37. Rosenbloom A.J., Pinsky M.R., Napoltano C. Suppression of cytokine-mediated beta2-integrin activation on circulating neutrophils in critically ill patients // Journal of Leukocyte Biology. 1999. Vol. 66, No. 1. P. 83–89.
38. Sakamoto Y., Mashiko K., Matsumoto H. [et al.]. Systemic inflammatory response syndrome scope at admission predicts injury severity, organ damage and serum neutrophil elastase production in trauma patients // The Nihon University Journal of Medicine. 2010. Vol. 77. P. 138–144.
39. Schauber J., Dorschner R. A., Coda A. B. [et al.]. Injury enhances TLR2 function and antimicrobial peptide expression through a Vitamin D-dependent mechanism // Journal of Clinical Investigation. 2007. Vol. 117, No. 3. P. 803–811.
40. Segaert S. Vitamin D regulation of cathelicidin in the skin: toward a renaissance of Vitamin D in dermatology? // Journal of Investigative Dermatology. 2008. Vol. 128, No. 4. P. 773–775.
41. Souza-Foseca-Guimaraes F., Parlato M., Fitting C. NK cell tolerance to TLR agonists mediated by regulatory T cells after polymicrobial sepsis // Journal of Immunology. 2012. Vol. 188, No. 12. P. 5850–5858.
42. Toubi E., Shoenfeld Y. The role of Vitamin D in regulating immune responses // Israel Medical Association Journal. 2010. Vol. 12, No. 3. P. 174–175.
43. Venet F., Chung C.S., Monneret G. Regulatory T cell population in sepsis and trauma // Journal of Leukocyte Biology. 2008. Vol. 83. P. 523–535.
44. Vincent J.L., Bihari D.J., Suter P. [et al.] The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee // Journal of the American Medical Association. 1995. Vol. 274, No. 8. P. 639–644.
45. Ward P.A. Immunosuppression in sepsis // Journal of the American Medical Association. 2011. Vol. 306, No. 23. P. 2618–2619.
46. Ward P.A. The dark side of C5a in sepsis // Nature Reviews Immunology. 2004. Vol. 4, No. 2. P. 133–142.
47. Wilkinson T.S., Morris A.C., Kefala K. Ventilator-associated pneumonia is characterized by excessive release of neutrophil proteases in the lung // Chest. 2012. Vol. 142, No. 6. P. 1427– 1432.
48. Yanagawa Y., Onoe K. Enhanced IL-10 production by TLR4- and TLR2-primed dendritic cells upon TLR restimulation // Journal of Immunology. 2007. Vol. 178, No. 10. P. 6173–6180.
49. Yim S., Dhawan P., Ragunath C., Christakos S., Diamond G. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25 dihydroxyVitamin D3 // Journal of Cystic Fibrosis. 2007. Vol. 6, No. 6. P. 403–410.
50. Zittermann A., Gummert J. F. Nonclassical Vitamin D actions // Nutrients. 2010. Vol. 2, No. 4. P. 408–425.


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