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

Introduction

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.

Methods

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.

Results

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

Conclusion

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.