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Circulating Levels of the Shed Scavenger Receptor sCD163 and Association with Outcome of Critically Ill Patients

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Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Purpose

CD163, a scavenger receptor for haptoglobin-hemoglobin complexes, is almost exclusively expressed by monocytes and macrophages and is shedded (as sCD163) by inflammatory stimuli. Thus, high serum levels of sCD163 predicted mortality in certain inflammatory diseases. We investigated baseline levels, time course of sCD163 levels and CD163 gene expression in relation to mortality and clinical complications in a large heterogeneous cohort of critically ill patients.

Methods

In this pre-planned secondary analysis of two randomized clinical studies, critically ill patients (n = 1657) were randomized to “conventional” (insulin administered only for blood glucose levels above 215 mg/dL) or “intensive” insulin therapy (glycemia maintained at 80–110 mg/dL) and compared with healthy controls (n = 112).

Results

Upon admission, critically ill patients had 1.6-fold higher sCD163 levels than controls (P < 0.0001). Long-stay patients (ICU stay >5 days), non-survivors and patients who developed liver dysfunction or kidney injury had higher baseline sCD163 levels. In multivariable analyses, elevated baseline sCD163 levels were independently associated with ICU mortality, liver dysfunction, and time to discharge from ICU and hospital. sCD163 further increased during ICU stay in patients who developed organ dysfunction and in non-survivors. Avoiding hyperglycemia with insulin slightly reduced circulating sCD163 levels. Hepatic CD163 gene expression in patients was higher than in controls (P = 0.002) and correlated positively with sCD163 levels (P = 0.345, P < 0.0001).

Conclusions

This study hallmarks the association of elevated sCD163 with organ dysfunction and adverse outcome of critical illness and may point to the liver as a potential source.

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Abbreviations

ADAM17:

a disintegrin and metalloprotease domain 17

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

AUC:

area under the curve

BMI:

body mass index

CI:

confidence interval

CIT:

conventional insulin therapy

CRP:

C-reactive protein

HPRT:

hypoxanthine-guanine phosphoribosyltransferase

ICU:

intensive care unit

IIT:

intensive insulin therapy

IQR:

interquartile range

LDH:

lactate dehydrogenase

LPS:

lipopolysaccharide

PT:

prothrombin time

ROC:

receiver operating characteristic curve

SIRS:

systemic inflammatory response syndrome

SD:

standard deviation

TACE:

TNF-α converting enzyme

TLR:

Toll-like receptor

TNF-α:

tumor-necrosis factor α

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Acknowledgements

We thank Kirsten Bank Petersen for excellent technical assistance.

CI received a Doctoral Fellowship of the Clinical Research Fund of the University Hospitals Leuven. GVdB by the University of Leuven, receives long-term structural research financing via the Methusalem program, funded by the Flemish Government.

Competing Interests

HM and Aarhus University have received royalties from IQ-products, the Netherlands.

The other authors declare that they have no competing interest.

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Authors and Affiliations

  1. Clinical Department and Laboratory of Intensive Care Medicine, Division Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Catherine Ingels, Pieter J. Wouters, Ilse Vanhorebeek & Greet Van den Berghe

  2. Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, 8000, Aarhus C, Denmark

    Holger J. Møller

  3. Immunoendocrine Research Unit, Aarhus University Hospital, Norrebrogade 42-44, 8000, Aarhus C, Denmark

    Troels K. Hansen

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  1. Catherine Ingels
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  2. Holger J. Møller
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  3. Troels K. Hansen
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  4. Pieter J. Wouters
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  5. Ilse Vanhorebeek
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  6. Greet Van den Berghe
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Correspondence to Greet Van den Berghe.

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Ingels, C., Møller, H.J., Hansen, T.K. et al. Circulating Levels of the Shed Scavenger Receptor sCD163 and Association with Outcome of Critically Ill Patients. J Clin Immunol 33, 619–629 (2013). https://doi.org/10.1007/s10875-012-9830-9

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  • DOI: https://doi.org/10.1007/s10875-012-9830-9

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