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Volume 3 Supplement 1


  • Poster presentation
  • Open Access

A high anti-inflammatory response is associated with intermediate-term mortality in patients with sepsis

  • 1,
  • 2, 3,
  • 1, 4,
  • 4,
  • 5,
  • 1, 4,
  • 2, 3, 6 and
  • 7
Intensive Care Medicine Experimental20153 (Suppl 1) :A79

  • Published:


  • Intensive Care Unit
  • Septic Shock
  • Severe Sepsis
  • Intensive Care Unit Admission
  • Sequential Organ Failure Assessment


Sepsis is characterized by a complex systemic inflammatory response to infection. While an overwhelming pro-inflammatory response is held responsible for early deaths, subsequent anti-inflammatory cytokine production may lead to immunosuppression and secondary infections. This has been suggested as a cause of intermediate-term deaths[1].


To study the relation between a persistent anti-inflammatory response and day 4-14 mortality in patients with severe sepsis and septic shock who have survived beyond the initial pro-inflammatory phase.


We included consecutive patients admitted with severe sepsis or septic shock to the Intensive Care Units (ICU) of 2 tertiary care centres in The Netherlands between January 2011 and July 2013 with a length of stay of at least 4 days. We excluded patients with prior immune deficiency. The anti-inflammatory response was assessed through interleukin (IL)-10 plasma concentrations on admission, day 2, and day 4 using BD™ CBA Flex Set system immunoassays. We categorized patients into 3 groups (low, moderate, high) based on day 4 IL-10 percentiles ( < 25th, 25-75th, >75th) and change from day 2 values. We measured IL-6 as marker of pro-inflammation. We used multivariable logistic regression analysis to study the relation with day 4-14 mortality and control for confounding.


We enrolled 485 patients; of these, we excluded 116 cases because of known immune deficiency and 19 cases because of missing plasma samples, leaving 350 subjects for analysis. A total of 148 (42%) patients were categorized as having a low anti-inflammatory response, 122 (35%) as moderate, and 80 (23%) as high. The groups were similar with respect to age, gender, and ICU length of stay (LOS), but patients with high anti-inflammatory response had higher Apache IV scores and were diagnosed with more abdominal and less pulmonary infections. Mortality between day 4 and 14 was 14%, 9% and 36% for patients with low, moderate, and high IL-10 levels, respectively (p= < 0.01). After adjustment for age, comorbidities, sequential organ failure assessment score, site of infection and IL-6 response in the first 4 days of ICU admission, a persistent high anti-inflammatory response on day 4 remained independently associated with increased mortality (crude odds ratio high vs. low 3.4; adjusted 2.8, 95% CI 1.4-5.7).


High anti-inflammatory response after 4 days is an independent risk factor for intermediate-term mortality in critically ill patients with sepsis.

Grant Acknowledgment

This study was performed within the Molecular diagnosis And Risk stratification of Sepsis (MARS) project (grant-04l-201).
Table 1

Patient characteristics.


Low IL-10 level (n = 148)

Moderate IL-10 level (n = 122)

High IL-10 level (n = 80)


Age, median (IQR)

65 (56-73)

62 (53-73)

66 (59-73)


Gender (male), n (%)

94 (64%)

75 (62%)

45 (56%)


Charlson Comorbidity Index, median (IQR)

4 (0-10)

4 (0-9)

5 (0-11)


Apache IV score, median (IQR)

82 (67-99)

83 (69-102)

87 (71-113)


ICU length of stay, median (IQR)

10 (6-17)

10 (7-19)

10 (7-19)


Total SOFA score day 3, median (IQR)

8 (6-10)

9 (7-11)

10 (8-13)

< 0.01

IL-6 day 4 (pg/ml)*, median (IQR)

3 (2.3-4)

3.9 (3.0-4.7)

4.7 (4-5.5)

< 0.01

Day-14 mortality, n (%)

21 (14%)

11 (9%)

29 (36%)

< 0.01

IQR=Interquartile range. SOFA = Sequential Organ Failure Assessment. Difference between groups (low, moderate, high) was tested by one-way ANOVA or Kruskal-Wallis test for continuous variables as appropriate. Differences between groups for categorical variables was tested for using a Chi-square test. * Log transformed

Authors’ Affiliations

Julius Center, University Medical Center Utrecht, Utrecht, Netherlands
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
Center for Infection and Immunity, Academic Medical Center, Amsterdam, Netherlands
Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands
Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
Intensive Care, University Medical Center Utrecht, Utrecht, Netherlands


  1. Hotchkiss RS, Monneret G, Payen D: Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013, 13 (12): 862-74. 10.1038/nri3552.PubMedPubMed CentralView ArticleGoogle Scholar


© Frencken et al.; 2015

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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.