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Published in: European Journal of Trauma and Emergency Surgery 3/2022

Open Access 11-04-2021 | Original Article

Acute alcohol consumption increases systemic endotoxin bioactivity for days in healthy volunteers—with reduced intestinal barrier loss in female

Authors: Ramona Sturm, Florian Haag, Andrea Janicova, Baolin Xu, Jan Tilmann Vollrath, Katrin Bundkirchen, Ildiko Rita Dunay, Claudia Neunaber, Ingo Marzi, Borna Relja

Published in: European Journal of Trauma and Emergency Surgery | Issue 3/2022

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Abstract

Objective

Trauma is the most common cause of death among young adults. Alcohol intoxication plays a significant role as a cause of accidents and as a potent immunomodulator of the post-traumatic response to tissue injury. Polytraumatized patients are frequently at risk to developing infectious complications, which may be aggravated by alcohol-induced immunosuppression. Systemic levels of integral proteins of the gastrointestinal tract such as syndecan-1 or intestinal fatty acid binding proteins (FABP-I) reflect the intestinal barrier function. The exact impact of acute alcohol intoxication on the barrier function and endotoxin bioactivity have not been clarified yet.

Methods

22 healthy volunteers received a precisely defined amount of alcohol (whiskey–cola) every 20 min over a period of 4 h to reach the calculated blood alcohol concentration (BAC) of 1‰. Blood samples were taken before alcohol drinking as a control, and after 2, 4, 6, 24 and 48 h after beginning with alcohol consumption. In addition, urine samples were collected. Intestinal permeability was determined by serum and urine values of FABP-I, syndecan-1, and soluble (s)CD14 as a marker for the endotoxin translocation via the intestinal barrier by ELISA. BAC was determined.

Results

Systemic FABP-I was significantly reduced 2 h after the onset of alcohol drinking, and remained decreased after 4 h. However, at 6 h, FABP-I significantly elevated compared to previous measurements as well as to controls (p < 0.05). Systemic sCD14 was significantly elevated after 6, 24 and 48 h after the onset of alcohol consumption (p < 0.05). Systemic FABP-I at 2 h after drinking significantly correlated with the sCD14 concentration after 24 h indicating an enhanced systemic LPS bioactivity. Women showed significantly lower levels of syndecan-1 in serum and urine and urine for all time points until 6 h and lower FABP-I in the serum after 2 h.

Conclusions

Even relative low amounts of alcohol affect the immune system of healthy volunteers, although these changes appear minor in women. A potential damage to the intestinal barrier and presumed enhanced systemic endotoxin bioactivity after acute alcohol consumption is proposed, which represents a continuous immunological challenge for the organism and should be considered for the following days after drinking.
Literature
1.
go back to reference NIS LeaT-DdS. 2017. Trauma Register DGU Jahresbericht 2017. NIS LeaT-DdS. 2017. Trauma Register DGU Jahresbericht 2017.
2.
go back to reference Sakran JV, Greer SE, Werlin E, McCunn M. Care of the injured worldwide: trauma still the neglected disease of modern society. Scand J Trauma Resusc Emerg Med. 2012;20:64.CrossRef Sakran JV, Greer SE, Werlin E, McCunn M. Care of the injured worldwide: trauma still the neglected disease of modern society. Scand J Trauma Resusc Emerg Med. 2012;20:64.CrossRef
3.
go back to reference Green RS, Kureshi N, Erdogan M. Legal consequences for alcohol-impaired drivers injured in motor vehicle collisions: a systematic review. Accid Anal Prev. 2015;80:106–16.CrossRef Green RS, Kureshi N, Erdogan M. Legal consequences for alcohol-impaired drivers injured in motor vehicle collisions: a systematic review. Accid Anal Prev. 2015;80:106–16.CrossRef
4.
go back to reference <Global status report on alcohol and health2018.pdf>. <Global status report on alcohol and health2018.pdf>.
5.
6.
go back to reference Organisation WH. 2018. Legal BAC limits by country. Organisation WH. 2018. Legal BAC limits by country.
7.
go back to reference Relja B, Menke J, Wagner N, Auner B, Voth M, Nau C, Marzi I. Effects of positive blood alcohol concentration on outcome and systemic interleukin-6 in major trauma patients. Injury. 2016;47:640–5.CrossRef Relja B, Menke J, Wagner N, Auner B, Voth M, Nau C, Marzi I. Effects of positive blood alcohol concentration on outcome and systemic interleukin-6 in major trauma patients. Injury. 2016;47:640–5.CrossRef
8.
go back to reference Wutzler S, Lustenberger T, Relja B, Lehnert M, Marzi I. Pathophysiology of multiple trauma: intensive care medicine and timing of treatment. Chirurg. 2013;84:753–8.CrossRef Wutzler S, Lustenberger T, Relja B, Lehnert M, Marzi I. Pathophysiology of multiple trauma: intensive care medicine and timing of treatment. Chirurg. 2013;84:753–8.CrossRef
9.
go back to reference Huber-Lang M, Gebhard F, Schmidt CQ, Palmer A, Denk S, Wiegner R. Complement therapeutic strategies in trauma, hemorrhagic shock and systemic inflammation - closing Pandora’s box? Semin Immunol. 2016;28:278–84.CrossRef Huber-Lang M, Gebhard F, Schmidt CQ, Palmer A, Denk S, Wiegner R. Complement therapeutic strategies in trauma, hemorrhagic shock and systemic inflammation - closing Pandora’s box? Semin Immunol. 2016;28:278–84.CrossRef
10.
go back to reference Wagner N, Akbarpour A, Mors K, Voth M, Stormann P, Auner B, Lehnert M, Marzi I, Relja B. Alcohol intoxication reduces systemic interleukin-6 levels and leukocyte counts after severe TBI compared with not intoxicated TBI patients. Shock. 2016;46:261–9.CrossRef Wagner N, Akbarpour A, Mors K, Voth M, Stormann P, Auner B, Lehnert M, Marzi I, Relja B. Alcohol intoxication reduces systemic interleukin-6 levels and leukocyte counts after severe TBI compared with not intoxicated TBI patients. Shock. 2016;46:261–9.CrossRef
11.
go back to reference Relja B, Hohn C, Bormann F, Seyboth K, Henrich D, Marzi I, Lehnert M. Acute alcohol intoxication reduces mortality, inflammatory responses and hepatic injury after haemorrhage and resuscitation in vivo. Br J Pharmacol. 2012;165:1188–99.CrossRef Relja B, Hohn C, Bormann F, Seyboth K, Henrich D, Marzi I, Lehnert M. Acute alcohol intoxication reduces mortality, inflammatory responses and hepatic injury after haemorrhage and resuscitation in vivo. Br J Pharmacol. 2012;165:1188–99.CrossRef
12.
go back to reference Jurkovich GJ, Rivara FP, Gurney JG, Fligner C, Ries R, Mueller BA, Copass M. The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma. JAMA. 1993;270:51–6.CrossRef Jurkovich GJ, Rivara FP, Gurney JG, Fligner C, Ries R, Mueller BA, Copass M. The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma. JAMA. 1993;270:51–6.CrossRef
13.
go back to reference Bala S, Tang A, Catalano D, Petrasek J, Taha O, Kodys K, Szabo G. Induction of Bcl-3 by acute binge alcohol results in toll-like receptor 4/LPS tolerance. J Leukoc Biol. 2012;92:611–20.CrossRef Bala S, Tang A, Catalano D, Petrasek J, Taha O, Kodys K, Szabo G. Induction of Bcl-3 by acute binge alcohol results in toll-like receptor 4/LPS tolerance. J Leukoc Biol. 2012;92:611–20.CrossRef
14.
go back to reference Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3–20 (quiz 1-2).CrossRef Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3–20 (quiz 1-2).CrossRef
15.
go back to reference Glatz JF, van der Vusse GJ. Cellular fatty acid-binding proteins: their function and physiological significance. Prog Lipid Res. 1996;35:243–82.CrossRef Glatz JF, van der Vusse GJ. Cellular fatty acid-binding proteins: their function and physiological significance. Prog Lipid Res. 1996;35:243–82.CrossRef
16.
go back to reference Pelsers MM, Namiot Z, Kisielewski W, Namiot A, Januszkiewicz M, Hermens WT, Glatz JF. Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility. Clin Biochem. 2003;36:529–35.CrossRef Pelsers MM, Namiot Z, Kisielewski W, Namiot A, Januszkiewicz M, Hermens WT, Glatz JF. Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility. Clin Biochem. 2003;36:529–35.CrossRef
17.
go back to reference Voth M, Duchene M, Auner B, Lustenberger T, Relja B, Marzi I. I-FABP is a novel marker for the detection of intestinal injury in severely injured trauma patients. World J Surg. 2017;41:3120–7.CrossRef Voth M, Duchene M, Auner B, Lustenberger T, Relja B, Marzi I. I-FABP is a novel marker for the detection of intestinal injury in severely injured trauma patients. World J Surg. 2017;41:3120–7.CrossRef
18.
go back to reference de Haan JJ, Lubbers T, Derikx JP, Relja B, Henrich D, Greve JW, Marzi I, Buurman WA. Rapid development of intestinal cell damage following severe trauma: a prospective observational cohort study. Crit Care. 2009;13:R86.CrossRef de Haan JJ, Lubbers T, Derikx JP, Relja B, Henrich D, Greve JW, Marzi I, Buurman WA. Rapid development of intestinal cell damage following severe trauma: a prospective observational cohort study. Crit Care. 2009;13:R86.CrossRef
19.
go back to reference Salim SY, Young PY, Churchill TA, Khadaroo RG. Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients. J Surg Res. 2017;209:258–65.CrossRef Salim SY, Young PY, Churchill TA, Khadaroo RG. Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients. J Surg Res. 2017;209:258–65.CrossRef
20.
go back to reference Cronk DR, Houseworth TP, Cuadrado DG, Herbert GS, McNutt PM, Azarow KS. Intestinal fatty acid binding protein (I-FABP) for the detection of strangulated mechanical small bowel obstruction. Curr Surg. 2006;63:322–5.CrossRef Cronk DR, Houseworth TP, Cuadrado DG, Herbert GS, McNutt PM, Azarow KS. Intestinal fatty acid binding protein (I-FABP) for the detection of strangulated mechanical small bowel obstruction. Curr Surg. 2006;63:322–5.CrossRef
21.
go back to reference Sekino M, Funaoka H, Sato S, Okada K, Inoue H, Yano R, Matsumoto S, Ichinomiya T, Higashijima U, Matsumoto S, Hara T. Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock: a preliminary study. J Crit Care. 2017;42:92–100.CrossRef Sekino M, Funaoka H, Sato S, Okada K, Inoue H, Yano R, Matsumoto S, Ichinomiya T, Higashijima U, Matsumoto S, Hara T. Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock: a preliminary study. J Crit Care. 2017;42:92–100.CrossRef
22.
go back to reference Rapraeger A, Jalkanen M, Bernfield M. Cell surface proteoglycan associates with the cytoskeleton at the basolateral cell surface of mouse mammary epithelial cells. J Cell Biol. 1986;103:2683–96.CrossRef Rapraeger A, Jalkanen M, Bernfield M. Cell surface proteoglycan associates with the cytoskeleton at the basolateral cell surface of mouse mammary epithelial cells. J Cell Biol. 1986;103:2683–96.CrossRef
23.
go back to reference Bartlett AH, Hayashida K, Park PW. Molecular and cellular mechanisms of syndecans in tissue injury and inflammation. Mol Cells. 2007;24:153–66.PubMed Bartlett AH, Hayashida K, Park PW. Molecular and cellular mechanisms of syndecans in tissue injury and inflammation. Mol Cells. 2007;24:153–66.PubMed
24.
go back to reference Wei S, Gonzalez Rodriguez E, Chang R, Holcomb JB, Kao LS, Wade CE, Group PS. Elevated syndecan-1 after trauma and risk of sepsis: a secondary analysis of patients from the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial. J Am Coll Surg. 2018;227:587–95.CrossRef Wei S, Gonzalez Rodriguez E, Chang R, Holcomb JB, Kao LS, Wade CE, Group PS. Elevated syndecan-1 after trauma and risk of sepsis: a secondary analysis of patients from the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial. J Am Coll Surg. 2018;227:587–95.CrossRef
25.
go back to reference Hailman E, Vasselon T, Kelley M, Busse LA, Hu MC, Lichenstein HS, Detmers PA, Wright SD. Stimulation of macrophages and neutrophils by complexes of lipopolysaccharide and soluble CD14. J Immunol. 1996;156:4384–90.PubMed Hailman E, Vasselon T, Kelley M, Busse LA, Hu MC, Lichenstein HS, Detmers PA, Wright SD. Stimulation of macrophages and neutrophils by complexes of lipopolysaccharide and soluble CD14. J Immunol. 1996;156:4384–90.PubMed
26.
go back to reference Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T, Finlay BB, Wright SD. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992;176:1665–71.CrossRef Frey EA, Miller DS, Jahr TG, Sundan A, Bazil V, Espevik T, Finlay BB, Wright SD. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992;176:1665–71.CrossRef
27.
go back to reference Jacque B, Stephan K, Smirnova I, Kim B, Gilling D, Poltorak A. Mice expressing high levels of soluble CD14 retain LPS in the circulation and are resistant to LPS-induced lethality. Eur J Immunol. 2006;36:3007–16.CrossRef Jacque B, Stephan K, Smirnova I, Kim B, Gilling D, Poltorak A. Mice expressing high levels of soluble CD14 retain LPS in the circulation and are resistant to LPS-induced lethality. Eur J Immunol. 2006;36:3007–16.CrossRef
28.
go back to reference Hacker G, Redecke V, Hacker H. Activation of the immune system by bacterial CpG-DNA. Immunology. 2002;105:245–51.CrossRef Hacker G, Redecke V, Hacker H. Activation of the immune system by bacterial CpG-DNA. Immunology. 2002;105:245–51.CrossRef
29.
go back to reference Meroni M, Longo M, Dongiovanni P. Alcohol or gut microbiota: who is the guilty? Int J Mol Sci. 2019;20:4568.CrossRef Meroni M, Longo M, Dongiovanni P. Alcohol or gut microbiota: who is the guilty? Int J Mol Sci. 2019;20:4568.CrossRef
30.
go back to reference von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Initiative S. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Initiative S. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.CrossRef
31.
go back to reference Oldenburger IB, Wolters VM, Kardol-Hoefnagel T, Houwen RHJ, Otten HG. Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease. APMIS. 2018;126:186–90.CrossRef Oldenburger IB, Wolters VM, Kardol-Hoefnagel T, Houwen RHJ, Otten HG. Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease. APMIS. 2018;126:186–90.CrossRef
32.
go back to reference Montagnana M, Danese E, Lippi G. Biochemical markers of acute intestinal ischemia: possibilities and limitations. Ann Transl Med. 2018;6:341.CrossRef Montagnana M, Danese E, Lippi G. Biochemical markers of acute intestinal ischemia: possibilities and limitations. Ann Transl Med. 2018;6:341.CrossRef
33.
go back to reference Frink M, Pape HC, van Griensven M, Krettek C, Chaudry IH, Hildebrand F. Influence of sex and age on mods and cytokines after multiple injuries. Shock. 2007;27:151–6.CrossRef Frink M, Pape HC, van Griensven M, Krettek C, Chaudry IH, Hildebrand F. Influence of sex and age on mods and cytokines after multiple injuries. Shock. 2007;27:151–6.CrossRef
34.
go back to reference Hundscheid IHR, Schellekens D, Grootjans J, Derikx JPM, Buurman WA, Dejong CHC, Lenaerts K. Females are more resistant to ischemia-reperfusion-induced intestinal injury than males: a human study. Ann Surg. 2018;272(6):1070–9.CrossRef Hundscheid IHR, Schellekens D, Grootjans J, Derikx JPM, Buurman WA, Dejong CHC, Lenaerts K. Females are more resistant to ischemia-reperfusion-induced intestinal injury than males: a human study. Ann Surg. 2018;272(6):1070–9.CrossRef
35.
go back to reference Leclercq S, Cani PD, Neyrinck AM, Starkel P, Jamar F, Mikolajczak M, Delzenne NM, de Timary P. Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects. Brain Behav Immun. 2012;26:911–8.CrossRef Leclercq S, Cani PD, Neyrinck AM, Starkel P, Jamar F, Mikolajczak M, Delzenne NM, de Timary P. Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects. Brain Behav Immun. 2012;26:911–8.CrossRef
36.
go back to reference Afshar M, Richards S, Mann D, Cross A, Smith GB, Netzer G, Kovacs E, Hasday J. Acute immunomodulatory effects of binge alcohol ingestion. Alcohol. 2015;49:57–64.CrossRef Afshar M, Richards S, Mann D, Cross A, Smith GB, Netzer G, Kovacs E, Hasday J. Acute immunomodulatory effects of binge alcohol ingestion. Alcohol. 2015;49:57–64.CrossRef
37.
go back to reference Bala S, Marcos M, Gattu A, Catalano D, Szabo G. Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS ONE. 2014;9:e96864.CrossRef Bala S, Marcos M, Gattu A, Catalano D, Szabo G. Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS ONE. 2014;9:e96864.CrossRef
38.
go back to reference de Jong WJ, Cleveringa AM, Greijdanus B, Meyer P, Heineman E, Hulscher JB. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial. Alcohol. 2015;49:65–70.CrossRef de Jong WJ, Cleveringa AM, Greijdanus B, Meyer P, Heineman E, Hulscher JB. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial. Alcohol. 2015;49:65–70.CrossRef
39.
go back to reference Lubbers T, Kox M, de Haan JJ, Greve JW, Pompe JC, Ramakers BP, Pickkers P, Buurman WA. Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model. Crit Care Med. 2013;41:1258–65.CrossRef Lubbers T, Kox M, de Haan JJ, Greve JW, Pompe JC, Ramakers BP, Pickkers P, Buurman WA. Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model. Crit Care Med. 2013;41:1258–65.CrossRef
40.
go back to reference Lambert JC, Zhou Z, Wang L, Song Z, McClain CJ, Kang YJ. Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. J Pharmacol Exp Ther. 2003;305:880–6.CrossRef Lambert JC, Zhou Z, Wang L, Song Z, McClain CJ, Kang YJ. Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. J Pharmacol Exp Ther. 2003;305:880–6.CrossRef
41.
go back to reference Pan Z, Zhou L, Hetherington CJ, Zhang D-E. Hepatocytes contribute to soluble CD14 production, and CD14 expression is differentially regulated in hepatocytes and monocytes. J Biol Chem. 2000;275:36430–5.CrossRef Pan Z, Zhou L, Hetherington CJ, Zhang D-E. Hepatocytes contribute to soluble CD14 production, and CD14 expression is differentially regulated in hepatocytes and monocytes. J Biol Chem. 2000;275:36430–5.CrossRef
Metadata
Title
Acute alcohol consumption increases systemic endotoxin bioactivity for days in healthy volunteers—with reduced intestinal barrier loss in female
Authors
Ramona Sturm
Florian Haag
Andrea Janicova
Baolin Xu
Jan Tilmann Vollrath
Katrin Bundkirchen
Ildiko Rita Dunay
Claudia Neunaber
Ingo Marzi
Borna Relja
Publication date
11-04-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Trauma and Emergency Surgery / Issue 3/2022
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-021-01666-4

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