Skip to content

Advertisement

Volume 18 Supplement 2

Sepsis 2014

  • Poster presentation
  • Open Access

Association of initial intracellular signalling pathway and cytokine level with early mortality in severe sepsis patients

  • KC Lie1,
  • D Widodo1,
  • S Lardo2,
  • Eppy3 and
  • R Sinto1
Critical Care201418(Suppl 2):P46

https://doi.org/10.1186/cc14049

Published: 3 December 2014

Keywords

Early MortalityIntracellular Signalling PathwayEmergency UnitSevere Sepsis PatientArmy Hospital

Introduction

Sepsis occurs as a result of systemic inflammatory process. The release of bacterial components to the systemic circulation leads to activation of inhibitor kappa B kinase (IKK)-β and nuclear factor kappa B (NF-κB) through phosphorylation and ubiquitination. Excessive inflammatory process with maladaptive host's immune response leads to organ dysfunctions and death [1, 2]. This study was designed to investigate association of the initial level of intracellular signalling pathway and cytokine involved in sepsis pathophysiology (that is, IKK-β, NF-κB, tumour necrosis factor (TNF)α) and 72-hour (early) mortality in severe sepsis patients.

Methods

A prospective cohort study was conducted in severe sepsis patients (aged 18 years and older) admitted to the Emergency Unit of Cipto Mangunkusumo Hospital, Persahabatan Hospital, and Gatot Subroto Indonesia Central Army Hospital, Jakarta, Indonesia. All blood samples for intracellular signalling pathway (that is, IKK-β, total NF-κB, phospho NF-κB) and cytokine (that is, TNFα) were collected and measured using the ELISA method during first 24 hours of inclusion. Patients' outcome was observed during first 72 hours after inclusion. Mann-Whitney test was used to analyse the median difference of IKK-β, total NF-κB, phospho NF-κB level in two groups based on 72-hour survival. The t test was used to analyse the mean difference of TNFα levels in both groups.

Results

Subjects consisted of 90 patients. Early mortality developed in 27 subjects. Baseline characteristics of survival and death subjects are shown in Table 1. The initial intracellular signalling pathway and cytokine parameters level are shown in Table 2. There was a significant higher median first 24 hours IKK-β and total NF-κB level in survival subjects compared with death subjects (P = 0.025 for median IKK-β and P = 0.036 for median total NF-κB). There was no significant difference of initial phospho NF-κB and TNFα level in survival and death subjects.
Table 1

Baseline characteristics of the subjects

Characteristic

Survival subjects (n= 63)

Death subjects (n= 27)

Mean age (years)

52.98 ± 15.38

50.19 ± 13.46

Sex

  

  Male

23 (36.5)

12 (44.4)

  Female

40 (63.5)

15 (55.6)

Sepsis severity

  

  Severe sepsis

42 (66.7)

13 (48.1)

  Septic shock

21 (33.3)

14 (51.9)

Mean APACHE II score

13.03 ± 5.27

14.37 ± 6.55

Comorbidity

  

  Without comorbidity

4 (6.3)

2 (7.4)

  With comorbidity(s)

59 (93.7)

25 (92.6)

Source of infection

  

  Respiratory tract

45 (71.4)

24 (88.9)

  Intraabdominal

4 (6.3)

1 (3.7)

  Skin and soft tissue

5 (7.9)

1 (3.7)

  Urinary tract

2 (3.1)

1 (3.7)

  ≥ 2 sources

7 (11.3)

0

Mean procalcitonin (pg/ml)

21.47 ± 44.30

30.26 ± 17.29

Mean baseline lactate (mmol/l)

3.10 ± 1.77

4.89 ± 2.57

Data presented as n (%) or mean ± standard deviation. APACHE, Acute physiology and chronic health evaluation.

Table 2

Initial intracellular signalling pathway and cytokine level based on 72-hour survival

Parameter

Survived subjects (n= 63)

Death subjects (n= 27)

P value

IKK-βa

0.10 (0.03)

0.12 (0,03)

0.025

Total NF-κBa

0.08 (0.08)

0.12 (0.08)

0.036

Phospho NF-κBa

0.10 (0.38)

0.33 (0.38)

0.579

TNFαb

9.10 (7.80)

10.91 (11.74)

0.393

aMedian (interquartile range) in optical density, Mann-Whitney test. bMean (standard deviation) in pg/ml, t test.

Conclusion

There is a significant lower initial IKK-β and total NF-κB level in severe sepsis patients surviving on 72-hour observation. There is a tendency of lower initial phospho NF-κB and TNFα level in severe sepsis patients surviving on 72-hour observation.

Authors’ Affiliations

(1)
Division of Tropical and Infectious Diseases, Department of Internal Medicine, Universitas Indonesia, Jakarta, Indonesia
(2)
Department of Internal Medicine, Gatot Subroto Indonesia Central Army Hospital, Jakarta, Indonesia
(3)
Department of Internal Medicine, Persahabatan Hospital, Jakarta, Indonesia

References

  1. Coldewey SM, Rogazzo M, Collino M, Patel NSA, Thiemermann C: Inhibition of IkB kinase reduces the multiple organ dysfunction caused by sepsis in the mouse. Dis Mode Mech 2013, 6: 1031-1042. 10.1242/dmm.012435View ArticleGoogle Scholar
  2. Liu SF, Malik AB: NFkB activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 2006, 290: L622-L645. 10.1152/ajplung.00477.2005View ArticlePubMedGoogle Scholar

Copyright

© Lie et al.; licensee BioMed Central Ltd. 2014

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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement