An Unbalanced Inflammatory Cytokine Response Is Not Associated With Mortality Following Sepsis: A Prospective Cohort Study.

Abstract

OBJECTIVE:

The prevailing theory of host response during sepsis states that an excessive production of pro-inflammatory mediators causes early deaths, whereas a predominantly anti-inflammatory response may lead to immunosuppression, secondary infection, and late deaths. We assessed inflammatory (im)balance by measuring pro-inflammatory interleukin-6 and anti-inflammatory interleukin-10 during three distinct time periods after sepsis, and assessed its association with mortality.

DESIGN:

Prospective observational cohort.

SETTING:

Two tertiary mixed ICUs in The Netherlands.

PATIENTS:

Consecutive patients presenting with severe sepsis or septic shock from 2011 to 2013.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We repeatedly measured plasma interleukin-6 and interleukin-10 concentrations using cytometric bead array. Poisson regression was used to analyze the relation between inflammatory markers measured on 1) ICU admission and day 4 mortality, 2) day 4 and day 28 mortality, and 3) ICU discharge and 1-year mortality. Secondary outcome was development of ICU-acquired infections. Among 708 patients, 86 (12%) died within 4 days, 140 (20%) died between days 4 and 28, and an additional 155 (22%) died before 1 year. Interleukin-6 and interleukin-10 levels were both independently associated with mortality, but the balance of this response as modelled by an interleukin-6 and interleukin-10 interaction term was not (relative risk, 0.99; 95% CI, 0.95-1.04 on admission; relative risk, 1.02; 95% CI, 0.98-1.06 on day 4; and relative risk, 1.12; 95% CI, 0.98-1.29 at ICU discharge). However, inflammatory imbalance on day 4 was associated with development of ICU-acquired infections (subdistribution hazard ratio, 0.87; 95% CI, 0.77-0.98).

CONCLUSIONS:

Although both interleukin-6 and interleukin-10 productions are associated with death, the balance of these inflammatory mediators does not seem to impact either early, intermediate, or late mortality in patients presenting to the ICU with sepsis.

• Authors: Jos F Frencken, Lonneke A van Vught, Linda M Peelen, David S Y Ong, Peter M C Klein Klouwenberg, Janneke Horn, Marc J M Bonten, Tom van der Poll, Olaf L Cremer, MARS Consortium
• Journal: Critical care medicine (Crit Care Med) Vol. 45 Issue 5 Pg. e493-e499 (May 2017) ISSN: 1530-0293 [Electronic] United States
• PMID: 28257334 (Publication Type: Journal Article, Multicenter Study, Observational Study)

Chemical References

• Cytokines
• IL10 protein, human
• IL6 protein, human
• Interleukin-6
• Interleukin-10

Topics

• APACHE
• Aged
• Cross Infection (epidemiology)
• Cytokines (metabolism)
• Female
• Hospital Mortality
• Hospitalization (statistics & numerical data)
• Humans
• Intensive Care Units (statistics & numerical data)
• Interleukin-10 (metabolism)
• Interleukin-6 (metabolism)
• Male
• Middle Aged
• Netherlands
• Prospective Studies
• Risk Factors
• Sepsis (epidemiology, immunology, mortality)
• Shock, Septic (immunology, mortality)
• Time Factors