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Lipopolysaccharide Binding Protein Is Down-Regulated During Acute Liver Failure

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Abstract

Background and Aims

Lipopolysaccharide binding protein (LBP) is involved in the modulation of acute liver injury and failure caused by acetaminophen (APAP). Although the biological activity of LBP is concentration dependent, little is known about its levels in acute liver failure.

Methods

Serum and hepatic LBP were measured in acute APAP-induced liver injury in mice. Serum LBP was measured in patients with acute liver failure from APAP and non-APAP causes.

Results

Interestingly, contrary to other diseases, serum and hepatic LBP levels decreased significantly in mice within 24 h after being subjected to APAP-induced injury compared to the control (1.6 ± 0.1 vs. 3.5 ± 1.6 μg/ml, respectively; P < 0.05). Similar decreases were noted in another mouse model of acute liver injury due to carbon tetrachloride. Among patients with acute liver failure due to APAP (n = 5) and non-APAP (n = 5) causes, admission LBP levels were decreased compared to those of healthy controls (5.4 ± 1.4 vs. 3.2 ± 0.2 μg/ml, normal vs. acute liver failure; P = 0.07). However, the levels were not associated with the etiology of acute liver failure or 3-week outcome.

Conclusions

Serum and hepatic LBP levels are significantly reduced early after the induction of severe acute liver injury/failure due to acetaminophen and other liver injuries. This reduction in LBP production is specific to acute liver failure and may be important in developing future diagnostic and therapeutic approaches for patients with acute liver failure.

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Abbreviations

LBP:

Lipoppolysaccharide binding protein

LPS:

Lipopolysaccharide

KO:

Knockout

APAP:

Acetaminophen 

CCL4 :

Carbon tetrachloride 

ALF:

Acute liver failure

ALFSG:

Acute Liver Failure Study Group

CRP:

C-reactive protein

MODS:

Multiple organ dysfunction syndrome

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Acknowledgments

We gratefully acknowledge the support provided by the Acute Liver Failure Study Group which was funded by NIH grant DK U-01 58369 from the National Institute of Diabetes, Digestive and Kidney Disease and the Veteran’s Administration Merit Award (G.L.S.).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Veterans Administration Ann Arbor Healthcare Systems, Ann Arbor, MI, USA

    Grace L. Su

  2. Department of Medicine, University of Michigan Medical School, 2215 Fuller Road, Ann Arbor, MI, 48105, USA

    Grace L. Su

  3. Department of Medicine, University of Michigan Medical School, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI, 49109, USA

    Robert J. Fontana & Kartik Jinjuvadia

  4. Department of Medicine, University of Michigan Medical School, 1510 MSRB I, 1150 West Medical Center Drive, Ann Arbor, MI, 49109, USA

    Jill Bayliss

  5. Department of Surgery, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI, USA

    Stewart C. Wang

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  1. Grace L. Su
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  2. Robert J. Fontana
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  3. Kartik Jinjuvadia
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  4. Jill Bayliss
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  5. Stewart C. Wang
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Correspondence to Grace L. Su.

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Su, G.L., Fontana, R.J., Jinjuvadia, K. et al. Lipopolysaccharide Binding Protein Is Down-Regulated During Acute Liver Failure. Dig Dis Sci 57, 918–924 (2012). https://doi.org/10.1007/s10620-012-2046-2

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  • DOI: https://doi.org/10.1007/s10620-012-2046-2

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