Association of initial intracellular signalling pathway and cytokine level with early mortality in severe sepsis patients
© Lie et al.; licensee BioMed Central Ltd. 2014
Published: 3 December 2014
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.
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.
Baseline characteristics of the subjects
Survival subjects (n= 63)
Death subjects (n= 27)
Mean age (years)
52.98 ± 15.38
50.19 ± 13.46
Mean APACHE II score
13.03 ± 5.27
14.37 ± 6.55
Source of infection
Skin and soft tissue
≥ 2 sources
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
Initial intracellular signalling pathway and cytokine level based on 72-hour survival
Survived subjects (n= 63)
Death subjects (n= 27)
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.
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