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Critical Care

Volume 18 Supplement 2

Sepsis 2014

Open Access

Proinflammatory versus anti-inflammatory response in sepsis patients: looking at the cytokines

  • D Anand1,
  • S Ray2,
  • S Bhargava1,
  • S Das1,
  • A Garg2,
  • S Taneja2,
  • D Dhar2 and
  • L Mohan Srivastava1
Critical Care201418(Suppl 2):P13

Published: 3 December 2014


Proinflammatory CytokineSupportive CareInstitutional Ethic CommitteeEarly DeathImmune Suppression


Despite improvements in supportive care, mortality rates in sepsis remain substantially high. Sepsis exhibits phases of enhanced inflammation, alternating with immune suppression with a resultant variant time point of mortality; yet no human study has correlated levels of cytokines to the timeline of mortality. Our study attempts to analyze the association of levels of proinflammatory and anti-inflammatory cytokines in sepsis with the timeline of death in terms of early (<5 days) versus late (>5 days) mortality, and day of death. We also assessed correlation of these cytokines with length of stay.


The study protocol was approved by Institutional Ethics Committee. Subjects were 74 consecutive patients with community-acquired severe sepsis/septic shock admitted to the ICU of a tertiary care superspeciality hospital. Blood samples drawn on days 1, 3 and 7 of admission were analysed for proinflammatory cytokine (TNFα) by chemiluminescent immunometric assay and anti-inflammatory cytokine (IL-10) by ELISA. Subjects were segregated on basis of: ratio of proinflammatory and anti-inflammatory mediators on day 1 of admission into patients with predominant proinflammatory or predominant anti-inflammatory response. Survival and time point of mortality into survivor, early mortality and late mortality groups. Statistical analyses were performed using SPSS version 17.


There were 37 patients each in predominant proinflammatory and predominant anti-inflammatory groups. The number of deaths was 11 and 17 respectively in these groups. However, there was significantly higher early mortality in the proinflammatory group as compared to the anti-inflammatory group (7 vs. 1, P = 0.0247). On the contrary, late deaths were significantly higher in the anti-inflammatory group as compared to the proinflammatory (16 vs. 4 P = 0.0017). The ratio of proinflammatory/anti-inflammatory cytokines (TNF/IL-10) on day 1 was significantly lower in patients of late death (n = 20) as compared to patients of early death (n = 8) and survivors (n = 46) as shown in Table 1. Further, the median day of death was significantly delayed in patients in the anti-inflammatory as compared to the proinflammatory group (20 vs. 5, P < 0.001). Length of hospital stay amongst survivors was significantly longer in the anti-inflammatory as compared to the proinflammatory group (23 vs. 10 P < 0.001).
Table 1

TNF/IL-10 ratio in study groups at different time points


Early death (≤ 5 days) (n= 8)

Late death (>5 days) (n= 20)

Survivors (n= 46)

P value

Day 1

1.81 (1.00 to 3.44)

0.50 (0.31 to 0.90)

1.22 (0.43 to 3.91)


Day 3

1.12 (0.50 to 3.91)

1.01(0.20 to 2.21)

2.5 (0.90 to 3.91)


Day 7


1.25 (0.59 to 2.38)

1.79 (0.75 to 3.90)


Data presented as median (IQR). Kruskal-Wallis test was performed for significance between three groups. *P < 0.05 considered significant.


Our preliminary data suggest that in sepsis, the ratio of proinflammatory/anti-inflammatory cytokines on day 1 is significantly associated with time point of mortality; hence, this ratio can be used to particularize management. Further studies are in progress to substantiate the role of proinflammatory and anti-inflammatory cytokines in this subset of patients. Moreover, since predominant anti-inflammatory response was associated with later death, role of immunomodulators in sepsis needs to be explored.

Authors’ Affiliations

Department of Biochemistry and Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi, India
Department of Critical Care and Emergency Medicine, Sir Ganga Ram Hospital, New Delhi, India


© Anand et al.; licensee BioMed Central Ltd. 2014

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. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.