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The human response to infection is associated with distinct patterns of interleukin 23 and interleukin 27 expression

Intensive Care Medicine volume 34, pages 683–691 (2008)Cite this article

Abstract

Objective

The development and progression of severe sepsis is related to a deficiency in pro-inflammatory cytokine production, characterised by lesser IFNγ levels, which are not explained by variations in levels of the main putative regulator of IFNγ, namely IL-12. As alternative regulators of IFNγ may be of greater importance in human sepsis, we investigated the hypothesis that the development of severe sepsis is related to variations in IL-18, IL-23 and IL-27 gene expression.

Design and setting

A prospective observational trial in a mixed intensive care unit (ICU) and hospital wards in a university teaching hospital.

Patients and participants

Sixty-two ICU patients with severe sepsis, 13 bacteraemic patients with no acute critical illness, and 10 healthy controls.

Measurements and results

All subjects were assayed for IL-18, IL-23 and IL-27 mRNA levels in peripheral blood. IL-27 mRNA levels distinguished between the three groups, with levels highest in the ICU group, intermediate in the bacteraemic group and lowest in the control group. IL-23 distinguished between the groups, with levels lowest in the ICU group. In late sepsis IL-23 and TNFα mRNA levels were directly related. IL-18 mRNA levels did not distinguish between the patient groups.

Conclusions

We conclude that the deficient pro-inflammatory response in patients with sepsis is expansive and includes deficient IL-23 and excessive IL-27 gene expression. This provides further evidence that upregulation of a cytokine-based immune response is beneficial in sepsis.

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Acknowledgements

Dr. Ross McManus is a Wellcome Trust/Health Research Board lecturer. We wish to acknowledge funding from the Higher Education Authority Programme for Research in Third Level Institutions.

Author information

Affiliations

  1. Department of Anaesthesia, St James’s Hospital, Dublin, Ireland

    Michael J. O’Dwyer, Mary White & Thomas Ryan

  2. Department of Clinical Medicine, Trinity College, Dublin, Ireland

    Michael J. O’Dwyer, Arun K. Mankan, Mathew W. Lawless, Dermot P. Kelleher & Ross McManus

  3. Department of Immunology-Haematology-Transfusion, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    Patrick Stordeur

  4. Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland

    Brian O’Connell

Authors
  1. Michael J. O’Dwyer
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  2. Arun K. Mankan
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  3. Mary White
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  4. Mathew W. Lawless
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  5. Patrick Stordeur
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  6. Brian O’Connell
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  7. Dermot P. Kelleher
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  8. Ross McManus
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  9. Thomas Ryan
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Correspondence to Thomas Ryan.

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Dr. Ryan and Dr. McManus are joint senior authors.

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O’Dwyer, M.J., Mankan, A.K., White, M. et al. The human response to infection is associated with distinct patterns of interleukin 23 and interleukin 27 expression. Intensive Care Med 34, 683–691 (2008). https://doi.org/10.1007/s00134-007-0968-5

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  • DOI: https://doi.org/10.1007/s00134-007-0968-5

Keywords

  • Sepsis syndrome
  • Cytokines
  • Reverse transcriptase polymerase chain reaction
  • Helper T-cells