VZL 2009, 78(4):135-142

Synthesis of Sterols in Polytrauma Injury

Pavel Vyroubal1, Zdeněk Zadák1, Radomír Hyšpler1, Alena Tichá1, Jaroslav Cerman2, Jiří Bajnárek1, Martin Hronek1, Eduard Havel2
1 Univerzita Karlova v Praze, Lékařská fakulta v Hradci Králové a Fakultní nemocnice, Gerontologická a metabolická klinika, Hradec Králové
2 Univerzita Karlova v Praze, Lékařská fakulta v Hradci Králové a Fakultní nemocnice, Chirurgická klinika, Hradec Králové

Jedná se o monocentrickou, prospektivní klinickou studii. Cílem práce je snaha o objasnění role hypocholesterolémie vznikající u nemocných v klinicky závažných stavech.

Materiál a metody: Do studie byla zařazena skupina nemocných, kteří utrpěli polytrauma (n = 19). Mimo standardní biochemická vyšetření bylo provedeno stanovení plazmatických hladin sterolů (beta-sitosterol, kampesterol, latosterol, skvalen), interleukinu 6 (IL-6), kortizolu. Byl proveden ACTH-test a dále byla stanovena funkční zdatnost granulocytů pomocí testu oxidativního vzplanutí granulocytů. Odběry byly provedeny v den přijetí, první, čtvrtý a osmý den po traumatu.

Výsledky: Ve sledované skupině došlo k statisticky významnému poklesu celkového cholesterolu (TC - total cholesterol) a LDL-cholesterolu s úpravou do výchozích hodnot v průběhu sledovaného období. Společně s poklesem celkového cholesterolu byl zaznamenán pokles v oblasti jeho syntézy (latosterol a poměr latosterol/cholesterol). Byla pozorována vysoce signifikantní negativní korelace mezi IL-6 a celkovým cholesterolem. Přestože nebyla zjištěna porucha funkce nadledvin, byla nalezena signifikantně pozitivní korelace poměru latosterol/cholesterol (jako ukazatele de novo syntézy cholesterolu) s kortizolem po ACTH stimulačním testu. V závislosti na plazmatické hladině TC byla prokázána statisticky významná porucha baktericidie leukocytů pomocí stimulovaného testu oxidativního vzplanutí granulocytů.

Závěr: U nemocných s polytraumatem dochází k poklesu endogenní syntézy cholesterolu. Míra syntézy cholesterolu negativně koreluje s plazmatickou hladinou IL-6. Míra endogenní syntézy cholesterolu pozitivně koreluje se syntézou kortizolu v nadledvinách a s baktericidní schopností granulocytů.

Keywords: Hypocholesterolémie; Hypolipoproteinémie; SIRS; Cytokiny; Polytrauma

The study was clinical, monocentric and prospective. The aim of the study was to elucidate the role and importance of hypocholesterolemia in polytrauma.

Material and Methods: A group of patients, who sustained polytrauma (n = 19), were recruited to the study. We performed the determination of sterols plasma levels and their precursors (beta-sitosterol, campesterol, lathosterol, skvalen), interleukin 6 (IL-6) and cortisol in the blood serum. The short version of ACTH stimulation test was performed. The oxidative burst of granulocytes was evaluated. The blood samples were taken on the day of admission, the first, the fourth and the eighth post-operative and post-traumatic day.

Results: There was a significant decline of total cholesterol (TC) and LDL cholesterol level with full recovery during observed period. There was a decline of cholesterol synthesis (lathosterol and lathosterol//cholesterol ratio) together with a decline of total cholesterol. There was a significantly negative correlation between IL-6 level and total cholesterol. Despite no confirmation of disturbance of adrenal function, there was a significantly positive correlation between lathosterol/cholesterol ratio (a de novo cholesterol synthesis marker) and cortisol level after the ACTH stimulation test. There was a significant breakdown of bactericidal function of granulocytes along with a decline of TC plasma level.

Conclusion: There was decline of endogenous cholesterol synthesis in polytrauma injury. The cholesterol synthesis rate was negatively influenced by IL-6 level. The rate of endogenous cholesterol synthesis positively correlated with cortisol production by the adrenals and with bactericidal function of granulocytes.

Keywords: Hypocholesterolemia; Hypolipoproteinemia; SIRS; Cytokine; Polytrauma

Received: June 24, 2009; Published: December 1, 2009  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Vyroubal, P., Zadák, Z., Hyšpler, R., Tichá, A., Cerman, J., Bajnárek, J., Hronek, M., & Havel, E. (2009). Synthesis of Sterols in Polytrauma Injury. Vojenské Zdravotnické Listy, 78(4), 135-142
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. ACTON, S. - RIGOTTI, A. - LANDSCHULZ, KT., et al. Identification of scavenger receptor SR-BI as a high-density lipoprotein receptor. Science, 1996, vol. 271, p. 518-520. Go to original source... Go to PubMed...
    2. ALTMANN, SW. - DAVIS, HR. - ZHU, I., et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science, 2004, vol. 303, p. 1201-1204. Go to original source... Go to PubMed...
    3. ALVAREZ, C. - RAMOS, A. Lipids, lipoproteins and apoproteins in serum during infection. Clin. Chem., 1986, vol. 32, p. 142-145. Go to original source... Go to PubMed...
    4. BIETRIX, F. - YAN, D. - NAUZE, M., et al. Accelerated lipid absorption in mice overexpressing intestinal SR-BI J. Biol. Chem., 2006, vol. 281, p. 7214-7219. Go to original source... Go to PubMed...
    5. BORKOWSKI, AJ. - LEVIN, S. - DELCROIX, C., et al. Blood cholesterol and hydrocortisone production in man: quantitative aspects of the utilization of circulating cholesterol by the adrenals at rest and under adrenocortocotropin stimulation. J. Clin. Invest., 1967, vol. 46, p. 797-811. Go to original source... Go to PubMed...
    6. BRASS, EP. - VETTER, HV. Interleukin-6, but not tumor necrosis factor - alpha, increases lipogenesis in rat hepatocyte primary cultures. Biochem. J., 1994, vol. 301, p. 193-197. Go to original source... Go to PubMed...
    7. DELGADO-RODRIGUES, M. - MEDINA-CUADROS, M. - MARTINEZ-GALLEGO, G., et al. Total cholesterol, HDL-cholesterol and risk of nosocomial infection: a prospective study in surgical patients. Infect. Control. Hosp. Epidemiol., 1997, vol. 18, p. 9-18. Go to original source... Go to PubMed...
    8. DRUML, W. - FISCHER, M. Cholesterol improves the utilization of parenteral lipid emulsions. Wien Klin. Wochenschr., 2003, vol. 115, no. 21/22, p. 767-774. Go to original source... Go to PubMed...
    9. ELLIOT, DC. - WILES, SE. Low lipid concentrations in critical illness: hypocholesterolemia among trauma patients. Crit. Care Med., 1997, vol. 25, p. 1437-1439. Go to original source... Go to PubMed...
    10. ETTINGER, WH. - VARMA, VK. - SORCI-THOMAS, M., et al. Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler. Thromb., 1994, vol. 14, p. 8-13. Go to original source... Go to PubMed...
    11. FEINGOLD, KR. - SOUED, M. - ADI, S., et al. Tumor necrosis factor increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. Diabetes, 1990, vol. 39, p. 1569-1574. Go to original source... Go to PubMed...
    12. FREUDENBERG, MA. - BOG-HANSEN, TC. - BACK, U., et al. Interaction of lipopolysaccharides with plasma high-density lipoprotein in rats. Infect. Immun., 1980, vol. 28, p. 373-380. Go to original source... Go to PubMed...
    13. GIBBONS, GF. - MITROPOULOS, KA. - MYANT, NB. Biochemistry of cholesterol. Amsterdam, New York, Oxford, Elsevier Biomedical Press, 1982.
    14. GIOVANNINI, I. - BOLDRINI, G. - CHIARLA, C., et al. Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients. Intensive Care Med., 1999, vol. 25, p. 748-751. Go to original source... Go to PubMed...
    15. GOLDFARB, RD. - PARKER, TS. - LEVINE, DM., et al. Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2003, vol. 284, p. R550-R557. Go to original source... Go to PubMed...
    16. GORDON, BR. - PARKER, TS. - LEVINE, DM., et al. Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients. Crit. Care Med., 2001, vol. 29, p. 1563-1568. Go to original source... Go to PubMed...
    17. GUI, D. - SPADA, PL. - DE GAETANO, A., et al. Hypocholesterolemie and risk of death in the critically ill surgical patient. Intensive Care Med., 1996, vol. 2, p. 790-794. Go to original source... Go to PubMed...
    18. HARADA, K. - SHIMANO, H. - KAWAKAMI, M., et al. Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblast. Biochem. Biophys. Res. Comm., 1990, vol. 172, p. 1022-1027. Go to original source... Go to PubMed...
    19. HARRIS, HW. - GRUNFELD, C. - FEINGOLD, KR., et al. Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. J. Clin. Invest., 1993, vol. 91, p. 1028-1034. Go to original source... Go to PubMed...
    20. HUBSCH, AP. - CASAS, AT. - DORAN, JE. Protective effects of reconstituted high-density lipoprotein in rabbit gram-negative bacteremia models. J. Lab. Clin. Med., 1995, vol. 126, p. 548-558. Go to PubMed...
    21. KRAMER, W. - GIRBIG, F. - CORSIERO, D., et al. Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane. J. Biol. Chem., 2005, vol. 280, p. 1306-1320. Go to original source... Go to PubMed...
    22. MURRAY, RK., et al. Harper's Biochemistry. 23rd ed. Appleton and Lange, a Publishing Division of Prentice-Hall International, Connecticut, 1993.
    23. NAULI, AM., et al. CD 36 is important for chylomicron formation and secretion and may mediate cholesterol uptake in the proximal intestine. Gastroenterology, 2006, vol. 131, p. 1197-1207. Go to original source... Go to PubMed...
    24. PAKJRT, D. - DORAN, JE. - KOSTER, F., et al. Antiinflammatory effect of reconstituted high-density lipoprotein during human endotoxemia. J. Exp. Med., 1996, vol. 184, p. 1601-1608. Go to original source... Go to PubMed...
    25. PANOUSIS, CG. - ZUCKERMAN, SH. Interferon-gamma induces downregulation of Tangier disease gene (ATP-binding-cassette transporter-1) in macrophage-derived foam cells. Arterioscler. Thromb. Vasc. Biol., 2000, vol. 20, p. 1565-1571. Go to original source... Go to PubMed...
    26. TIETGE, UJ. - MAUGEAIS, C. - CAIN, W., et al. Overexpression of secretory phospholipase A2 caused rapid catabolism and altered tissue uptake of high-density lipoprotein cholesterol ester and lipoprotein A-1. J. Biol. Chem., 2000, vol. 275, p. 10077-10084. Go to original source... Go to PubMed...
    27. VAN DER VOORT, PH. - GERRITSEN, RT. - BAKKER, AJ., et al. HDL-cholesterol level and cortisol response to synacten in critically ill patients. Intensive Care Med., 2003, vol. 29, p. 2199-2203. Go to original source... Go to PubMed...
    28. WINDLER, E. - EWERS-GRABOV, U. - THIERY, J., et al. The prognostic value of hypocholesterolemia in hospitalized patients. Clin. Invest., 1994, vol. 72, p. 939-943. Go to original source... Go to PubMed...
    29. WOLFRAM, G. - ECKARD, J. - OLLNER, N. Disturbances of lipoprotein and fatty acid metabolism in patients with heavy injuries. Wien Klin. Wochenschr., 1980, vol. 58, p. 1327-1337. Go to original source... Go to PubMed...
    30. YAGUCHI, H. - TSUTSUMI, K. - SHIMONO, K., et al. Involvement of high-density lipoprotein as substrate cholesterol for steroidogenesis by bovine adrenal fasciculoreticularis cells. Life Sci., 1998, vol. 62, p. 1387-1395. Go to original source... Go to PubMed...

    Return to the content