Do plasma cytokine levels correlate with survival in septic patients?

Introduction

The presence of circulating bacteria or bacterial products, such as endotoxin, leads to systemic release of cytokines, a hallmark of septic shock. Proinflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1, IL-8, IL-6, and interferon-γ) are postulated to play a major role in the pathogenesis of the syndrome. A lot of study show that the presence of circulating cytokines has been found in patients with documented bacteremia or with signs of sepsis, often correlating with the severity of disease. The aim of the present study was to measure these inflammatory mediators (TNF-α, IL-6, IL-10 and nitric oxide) in different phases of septic patients, polytrauma and health volunteers to demonstrate that these mediators play a role in the pathogenesis of sepsis but do not serve as a prognostic marker.

Methods

Patients: the study sample included 19 patients with pulmonary sepsis; eight critically ill patients suffering from major tissue injury due to polytrauma, admitted in the medical intensive care unit; and 16 healthy controls. The criteria for inclusion in the group with sepsis were according to criteria of American College of Chest Physicians/Society of Critical Care Medicine Consensus. All septic patients were monitored using a pulmonary artery catheter (93A-431-75F Baxter) and the sepsis phases were separated using the hemodynamic criteria. This study was approved by the ethical council of the Hospital. Informed consent was obtained from all patients or next-of-kin. The samples were obtained in the Hospital Municipal Miguel Couto and the Hospital Universitário Clementino Fraga Filho (HUCFF).

Measurements of TNF-α, IL-6, IL-10 and nitric oxide concentrations: after inclusion criteria, blood samples (5 ml) were collected into sterile tubes containing disodium ethylenediaminetetra-acetic acid (EDTA). Plasma was separated by centrifugation, aliquoted, and frozen (-20°C) until assayed for cytokines. Plasma TNF-α, IL-6, IL-10 and nitric oxide concentrations were measured by enzyme-liked immunosobent assay (ELISA; Pharmingen, San Diego, USA) according to the manufacturer's instructions.

Results

We noted that there were no difference in the measurements of interleukin in the different phases of septic patients and no difference with the polytrauma group and the healthy volunteers. There were no correlations with release of interleukin and the antibiotic used in septic patients. The only measurement that had correlation with the severity of the sepsis was the IL-6, in the phase D that corresponds with septic shock.

Conclusion

Our findings contradict those from a number of earlier studies that correlated severity of sepsis and plasma levels of cytokines. Moreover, the chances of detecting elevated cytokine levels during severe infections are limited by their half -lives. Both TNF and IL-6 may decline despite persistence or even increased severity sepsis. When cytokines were first discovered, it was generally assumed that their presence in the circulation signaled pathology. As we noted, there is a considerable interindividual variation in cytokine production. Age, gender, or pre-existing disease could be the explanation of these variations. Despite cytokines play a role in the pathogenesis of sepsis, their measurement does not serve as a marker of infection disease and does not discriminate the severity of the inflammatory infectious response.