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

Abstract

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)-beta and nuclear factor kappa B (NF-kappaB) 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-beta, NF-kappaB, tumour necrosis factor (TNF)alpha) and 72-hour (early) mortality in severe sepsis patients. Method(s): 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-beta, total NF-kappaB, phospho NF- kappaB) and cytokine (that is, TNFalpha) 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-beta, total NF-kappaB, phospho NF- kappaB level in two groups based on 72-hour survival. The t test was used to analyse the mean difference of TNFalpha levels in both groups. Result(s): 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-beta and total NF-kappaB level in survival subjects compared with death subjects (P = 0.025 for median IKK-beta and P = 0.036 for median total NF-kappaB). There was no significant difference of initial phospho NF-kappaB and TNFalpha level in survival and death subjects. Conclusion(s): There is a significant lower initial IKK-beta and total NF-kappaB level in severe sepsis patients surviving on 72-hour observation. There is a tendency of lower initial phospho NF-kappaB and TNFalpha level in severe sepsis patients surviving on 72-hour observation. (Table Presented).