Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS‐Binding Protein in Patients with Severe Sepsis and Septic Shock
Abstract
Plasma endotoxin and lipopolysaccharide-binding protein (LBP) levels were measured in a group of 253 patients at the onset of severe sepsis and/or septic shock. Endotoxin levels were significantly greater than control levels (n=33; mean +/- SD, 5.1+/-7.3 pg/mL) in 78.3% of patients. Median endotoxin levels in patients with sepsis were 300 pg/mL (25%-75% interquartile range, 110-726 pg/mL). LBP levels were elevated in 97% of patients compared with normal control values of 4.1+/-1.65 microgram/mL. Median LBP levels in patients with sepsis were 31.2 microgram/mL (interquartile range, 22.5-47.7 microgram/mL). Median endotoxin levels at study entry were more highly elevated (515 vs. 230 pg/mL; P<.01), and LBP levels were less highly elevated (28.0 vs. 33.2 microgram/mL; P<.05) in nonsurvivors than survivors over the 28-day study period. No correlation was found between endotoxin and LBP levels. The quantitative level of both endotoxin and LBP may have prognostic significance in patients with severe sepsis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In sepsis, blood endotoxin levels can be very high, up to 500 pg/ml.
“blood endotoxin levels can be very high (up to 500 pg/ml [13])”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [13]
Cites
Bone, R. C., BALK, R. A., Cerra, F. B., Dellinger, R. P., Fein, A. M., Knaus, W. A., Schein, R. M. H., & Sibbald, W. J. (1992) · CHEST Journal · doi:10.1378/chest.101.6.1644 · Cited by 13,192 · see citing works
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference
(1992) · Critical Care Medicine · doi:10.1097/00003246-199206000-00025 · Cited by 5,091 · see citing works
Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., & Gusovsky, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10689 · Cited by 1,924 · see citing works
Pathogenetic Mechanisms of Septic Shock
Epstein, F. H., & Parrillo, J. E. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282008 · Cited by 1,548 · see citing works
Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 ( Tlr4 )
Qureshi, S. T., Larivière, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P., & Malo, D. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.4.615 · Cited by 1,525 · see citing works
Bone, R. C. (1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-115-6-457 · Cited by 1,357 · see citing works
Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling
Yang, R.-B., Mark, M., Gray, A., Huang, A., Xie, M.-H., Zhang, M., Goddard, A., Wood, W., Gurney, A., & Godowski, P. (1998) · Nature · doi:10.1038/26239 · Cited by 1,319 · see citing works
The cardiovascular response of normal humans to the administration of endotoxin.
Suffredini, A., Fromm, R., Parker, M., Brenner, M., Kovacs, J., Wesley, R., & Parrillo, J. (1989) · New England Journal of Medicine · doi:10.1056/nejm198908033210503 · Cited by 1,133 · see citing works
Plasma Cytokine and Endotoxin Levels Correlate with Survival in Patients with the Sepsis Syndrome
Casey, L. C., Balk, R. A., & Bone, R. C. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-119-8-199310150-00001 · Cited by 1,053 · see citing works
Endotoxin signal transduction in macrophages
Sweet, M. J., & Hume, D. A. (1996) · Journal of Leukocyte Biology · doi:10.1002/jlb.60.1.8 · Cited by 795 · see citing works
Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide
Kirschning, C. J., Wesche, H., Merrill Ayres, T., & Rothe, M. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.11.2091 · Cited by 753 · see citing works
Endotoxemia in Human Septic Shock
Danner, R. L., Elin, R. J., Hosseini, J. M., WESLEY, R. A., Reilly, J., & Parillo, J. E. (1991) · CHEST Journal · doi:10.1378/chest.99.1.169 · Cited by 655 · see citing works
Stuber, F. E., Petersen, M., Bokelmann, F., & Schade, U. F. (1996) · Critical Care Medicine · doi:10.1097/00003246-199603000-00004 · Cited by 549 · see citing works
LPS-binding proteins and receptors
Fenton, M. J., & Golenbock, D. T. (1998) · Journal of Leukocyte Biology · doi:10.1002/jlb.64.1.25 · Cited by 480 · see citing works
Selected Treatment Strategies for Septic Shock Based on Proposed Mechanisms of Pathogenesis
Natanson, C., Hoffman, W. D., Suffredini, A. F., Eichacker, P. Q., & Danner, R. L. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-120-9-199405010-00009 · Cited by 440 · see citing works
Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection
Jack, R. S., Fan, X., Bernheiden, M., Rune, G. M., Ehlers, M., Weber, A., Kirsch, G., Mentel, R., Fürll, B., Freudenberg, M. A., et al. (1997) · Nature · doi:10.1038/39622 · Cited by 345 · see citing works
LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.
Lamping, N., Dettmer, R., Schröder, N. W. J., Pfeil, D., Hallatschek, W., Burger, R., & Schumann, R. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2338 · Cited by 345 · see citing works
Endotoxemia: Methods of detection and clinical correlates
Hurley, J. C. (1995) · Clinical Microbiology Reviews · doi:10.1128/cmr.8.2.268 · Cited by 318 · see citing works
Goldie, A. S. (1995) · JAMA · doi:10.1001/jama.274.2.172 · Cited by 294 · see citing works
Shock and Multiple-Organ Dysfunction after Self-Administration of Salmonella Endotoxin
da Silva, A. M. T., Kaulbach, H. C., Chuidian, F. S., Lambert, D. R., Suffredini, A. F., & Danner, R. L. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282005 · Cited by 276 · see citing works
Treatment of Gram-negative septic shock with an immunoglobulin preparation
SCHEDEL, I., Dreikhausen, U., Nentwig, B., HÖCKENSCHNIEDER, M., Rauthmann, D., Balikcioglu, S., Coldewey, R., & Deicher, H. (1991) · Critical Care Medicine · doi:10.1097/00003246-199109000-00003 · Cited by 238 · see citing works
Lipopolysaccharide-induced lethality and cytokine production in aged mice
Tateda, K., Matsumoto, T., Miyazaki, S., & Yamaguchi, K. (1996) · Infection and Immunity · doi:10.1128/iai.64.3.769-774.1996 · Cited by 235 · see citing works
Catalytic Properties of Lipopolysaccharide (LPS) Binding Protein
Yu, B., & Wright, S. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4100 · Cited by 195 · see citing works
Endotoxemia associated with cardiopulmonary bypass
Rocke, D. A., Gaffin, S. L., Wells, M., Koen, Y., & Brock‐Utne, J. G. (1987) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(19)37043-6 · Cited by 178 · see citing works
Parsons, P. E., Worthen, G. S., Moore, E. E., Tate, R. M., & Henson, P. M. (1989) · American Review of Respiratory Disease · doi:10.1164/ajrccm/140.2.294 · Cited by 178 · see citing works
Wurfel, M. M., Monks, B. G., Ingalls, R. R., Dedrick, R. L., Delude, R. L., Zhou, D., Lamping, N., Schumann, R. R., Thieringer, R., Fenton, M. J., et al. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.12.2051 · Cited by 173 · see citing works
Sensitivity of Limulus amebocyte lysate (LAL) to LAL-reactive glucans
Roslansky, P. F., & Novitsky, T. J. (1991) · Journal of Clinical Microbiology · doi:10.1128/jcm.29.11.2477-2483.1991 · Cited by 155 · see citing works
Wortel, C. H., Möhlen, M. A. M. V. D., van Deventer, S. J. H., Sprung, C. L., Jastremski, M., Lubbers, M. J., Smith, C. R., Allen, I. E., & ten Cate, J. W. (1992) · The Journal of Infectious Diseases · doi:10.1093/infdis/166.6.1367 · Cited by 107 · see citing works
Cellular Binding of Soluble CD14 Requires Lipopolysaccharide (LPS) and LPS-binding Protein
Tapping, R. I., & Tobias, P. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.23157 · Cited by 104 · see citing works
Relative concentrations of endotoxin-binding proteins in body fluids during infection
Opal, S. M., Palardy, J., MARRA, M. N., McKelligon, B. M., Scott, R. W., & Fisher, C. J. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91767-1 · Cited by 95 · see citing works
Self-citationCD14 and tolerance to lipopolysaccharide: biochemical and functional analysis.
Labéta, M. O., Durieux, J. J., Spagnoli, G. C., Fernández, N., Wijdenes, J., & Herrmann, R. (1993) · PubMed Central · Cited by 78 · see citing works
Limulus amebocyte lysate (LAL) detection of endotoxin in human blood
Novitsky, T. J. (1994) · Journal of Endotoxin Research · doi:10.1177/096805199400100407 · Cited by 76 · see citing works
Dual effects of soluble CD14 on LPS priming of neutrophils
Troelstra, A., Giepmans, B. N. G., van Kessel, K. P. M., et al. (1997) · Journal of Leukocyte Biology · doi:10.1002/jlb.61.2.173 · Cited by 73 · see citing works
Hurley, J. C. (1994) · Journal of Clinical Microbiology · doi:10.1128/jcm.32.9.2120-2127.1994 · Cited by 57 · see citing works
Special Collection and Storage Tubes for Blood Endotoxin and Cytokine Measurements
Redl, H., Bahrami, S., Leichtfried, G., & Schlag, G. (1992) · Clinical Chemistry · doi:10.1093/clinchem/38.5.764 · Cited by 37 · see citing works
Nys, M., Damas, P., Joassin, L., et al. (1993) · Annals of Surgery · doi:10.1097/00000658-199303000-00013 · Cited by 29 · see citing works
Kirschning, C., Unbehaun, A., Fiedler, G., Hallatschek, W., Lamping, N., Pfeil, D., & Schumann, R. R. (1997) · Immunobiology · doi:10.1016/s0171-2985(97)80033-2 · Cited by 27 · see citing works
Lengacher, S., Jongeneel, C. V., Roy, D. L., et al. (1997) · PubMed · Cited by 24 · see citing works
Hyperlipidemic Response to Endotoxin - a Part of the Host-defence Mechanism
Liao, W., & Florén, C. (1993) · Scandinavian Journal of Infectious Diseases · doi:10.3109/00365549309008562 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans
Arunachalam, P. S., Wimmers, F., Mok, C. K. P., Perera, R. A. P. M., Scott, M., Hagan, T., Sigal, N., Feng, Y., Bristow, L., Tak-Yin Tsang, O., et al. (2020) · Science · doi:10.1126/science.abc6261 · Cited by 1,186 · see citing works
Opal, S. M., Laterre, P.-F., Francois, B., LaRosa, S. P., Angus, D. C., Mira, J.-P., Wittebole, X., Dugernier, T., Perrotin, D., Tidswell, M., et al. (2013) · JAMA · doi:10.1001/jama.2013.2194 · Cited by 812 · see citing works
Self-citationDellinger, R. P., Bagshaw, S. M., Antonelli, M., Foster, D. M., Klein, D. J., Marshall, J. C., Palevsky, P. M., Weisberg, L. S., Schorr, C. A., Trzeciak, S., et al. (2018) · JAMA · doi:10.1001/jama.2018.14618 · Cited by 502 · see citing works
Ancuta, P., Kamat, A., Kunstman, K. J., Kim, E.-Y., Autissier, P., Wurcel, A., Zaman, T., Stone, D., Mefford, M., Morgello, S., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002516 · Cited by 499 · see citing works
The endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457 · see citing works
Metabolic endotoxemia with obesity: Is it real and is it relevant?
Boutagy, N. E., McMillan, R. P., Frisard, M. I., & Hulver, M. W. (2016) · Biochimie · doi:10.1016/j.biochi.2015.06.020 · Cited by 413 · see citing works
Endotoxemia—menace, marker, or mistake?
Munford, R. S. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ru0316-151r · Cited by 219 · see citing works
Selkirk, G. A., McLellan, T. M., Wright, H. E., & Rhind, S. G. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00917.2007 · Cited by 170 · see citing works
Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies
Barochia, A., Solomon, S., Cui, X., Natanson, C., & Eichacker, P. Q. (2011) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2011.558190 · Cited by 169 · see citing works
Intracellular Lipopolysaccharide Sensing as a Potential Therapeutic Target for Sepsis
Pfalzgraff, A., & Weindl, G. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.01.001 · Cited by 139 · see citing works
Chen, J., Lai, J., Yang, L., Ruan, G., Chaugai, S., Ning, Q., Chen, C., & Wang, D. W. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13386 · Cited by 120 · see citing works
Roberts, J., Suckling, C., Peedle, G., Murphy, J., Dawkins, T., & Roberts, M. (2016) · Nutrients · doi:10.3390/nu8110733 · Cited by 99 · see citing works
“LPS concentrations at or above these levels have been more commonly associated in patients with Crohn’s disease [11] and sepsis [12].”
BackgroundKnox, E. G., Aburto, M. R., Tessier, C., Nagpal, J., Clarke, G., O’Driscoll, C. M., & Cryan, J. F. (2022) · iScience · doi:10.1016/j.isci.2022.105648 · Cited by 97 · see citing works
Stabilin Receptors Clear LPS and Control Systemic Inflammation
Cabral, F., Al-Rahem, M., Skaggs, J., Thomas, T. A., Kumar, N., Wu, Q., Fadda, P., Yu, L., Robinson, J. M., Kim, J., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103337 · Cited by 38 · see citing works
- Authors
- Opal, S. M., Scannon, P. J., Vincent, J., White, M., Carroll, S. F., Palardy, J. E., Parejo, N. A., Pribble, J. P., & Lemke, J. H.
- Affiliations
- Brown University (US)
- XOMA (United States) (US)
- Université Libre de Bruxelles (BE)
- University of Iowa (US)
- Corresponding author
- Opal, Steven M.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-11
- Volume
- 180
- Issue
- 5
- Pages
- 1584-1589
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2147383865
- Cited by
- 609
- References
- 39
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 26 · 2023: 26 · 2022: 28 · 2021: 31 · 2020: 35 · 2019: 33 · 2018: 12 · 2017: 26 · 2016: 30 · 2015: 32 · 2014: 17 · 2013: 34 · 2012: 21
- FWCI
- 9.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- lipopolysaccharide, lipopolysaccharide-binding protein, endotoxin, severe sepsis, septic shock, prognostic factors, mortality prediction, plasma endotoxin levels
- MeSH terms
- Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Adult, Aged, Carrier Proteins, Endotoxins, Female, Humans, Lipopolysaccharides, Male, Membrane Glycoproteins, Middle Aged, Prognosis, Shock, Septic, Fungemia, Bacteremia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review