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Volume 3 Supplement 1

ESICM LIVES 2015

  • Poster presentation
  • Open Access

Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways

  • 1, 2,
  • 1, 2,
  • 1,
  • 1, 2,
  • 1, 2 and
  • 1, 2
Intensive Care Medicine Experimental20153 (Suppl 1) :A820

https://doi.org/10.1186/2197-425X-3-S1-A820

  • Published:

Keywords

  • Interferon Gamma
  • Grant Acknowledgment
  • Overnight Hospital Stay
  • Donor PBMCs
  • Control Peripheral Blood

Introduction

The post-operative period is characterised by increased IL-6 production and clinical features of immune suppression. In vitro anti-inflammatory actions of IL-6 are mediated through suppression of interferon gamma (IFNγ) [1]. The clinical significance of IL-6 in mediating post-operative immune suppression remains unclear.

Objectives

To evaluate the role of IL-6 pathways in post-operative immune suppression and the reversibility of this phenomenon.

Methods

Patients over 45 years old undergoing elective surgery involving the gastrointestinal tract and requiring at least an overnight hospital stay were recruited. The primary outcome was hospital-acquired infection. IL-6 and IFNγ levels were assayed using ELISA preoperatively and at 24 and 48 hours. Pooled healthy control peripheral blood mononuclear cells (PBMCs) were cultured in perioperative serum and CD14+HLA-DR (mHLA-DR) geometric mean florescent intensity (MFI) measured in the presence and absence of interferon gamma (IFNγ) and IL-6 neutralising antibody. Data were analysed with non-parametric statistics.

Results

119 patients were recruited and 44 (37%) developed a post-operative infection a median of 9 (IQR 5-11) days postoperatively (Figure 1). IL-6 levels increased from baseline to 24 hours postoperatively (P < 0.0001, Figure 1A) but were then unchanged between 24 and 48 hours (P = 0.06, Figure 1B). Postoperative IL-6 levels correlated with the duration of the procedure (P = 0.009). Higher preoperative IL-6 levels were observed in patients with cancer (P = 0.02). IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with the later occurrence of infectious complications. This pattern remained similar after adjustment for baseline characteristics. Healthy donor PBMCs incubated with postoperative serum downregulated mHLA-DR MFI when compared with serum from baseline (n = 8, p = 0.008). Culturing in the presence of IFNγ 250IU (n = 4) prevented this decrease whereas culturing in the presence of IL-6 neutralising antibody 15ng/ml (n = 8) did not.

Figure 1

Conclusions

IL-6 levels increase following major surgery and are associated with an increased susceptibility to post-operative infections. Serum obtained from post-operative patients induces an immunosuppressive response through an IL-6 independent pathways which is reversible with IFNγ treatment.

Grant Acknowledgment

The National Institute of Academic Anaesthesia (NIAA)
Table 1

Characteristics of patients developing infections and those remaining infection free following scheduled abdominal surgery.

 

Infection

Infection free

PValue

 

N = 44 (37%)

N = 75 (63%)

 

Age (years)

66 (59 - 75)

64 (56 - 71)

0.19

Male sex (%)

27 (61)

47 (63)

0.89

Diabetes (%)

8 (18)

12 (16)

0.76

Current smokers (%)

10 (23)

14 (19)

0.60

Cancer diagnosis (%)

24 (55)

53 (71)

0.07

Preoperative Immunosuppression (%)

6 (14)

10 (14)

>0.99

Duration of operation (minutes)

243 (176 - 312)

195 (142 - 295)

0.06

Data are described as median with interquartile range with percentages in parenthesis

Authors’ Affiliations

(1)
Barts & the London School of Medicine, QMUL, William Harvey Research Institute, London, United Kingdom
(2)
Barts Health NHS Trust, Adult Critical Care Unit, London, United Kingdom

References

  1. Diehl S, et al: The two faces of IL-6 on Th1/Th2 differentiation. Mol Immunol. 2002, 39 (9): 531-6. 10.1016/S0161-5890(02)00210-9. DecPubMedView ArticleGoogle Scholar

Copyright

© Longbottom et al.; 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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