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Critical Care Medicine:
doi: 10.1097/CCM.0000000000000100
Feature Articles

Immunological Characterization of Compensatory Anti-Inflammatory Response Syndrome in Patients With Severe Sepsis: A Longitudinal Study*

Gomez, Henry G. MS1; Gonzalez, Sandra M. BS1; Londoño, Jessica M. MD2; Hoyos, Natalia A. MD2; Niño, Cesar D. MD2; Leon, Alba L. BS2,3; Velilla, Paula A. MS, SD1,4; Rugeles, Maria T. MS, SD1,4; Jaimes, Fabián A. MD, MS, PhD2,5,6

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Abstract

Objectives:

To perform a complete immunological characterization of compensatory anti-inflammatory response syndrome in patients with sepsis and to explore the relationship between these changes and clinical outcomes of 28-day mortality and secondary infections.

Design:

Prospective single-center study conducted between April 2011 and December 2012.

Setting:

ICUs from Hospital Universitario San Vicente Fundación at Medellin, Colombia.

Patients:

One hundred forty-eight patients with severe sepsis.

Interventions:

None.

Measurements and Main Results:

At days 0, 1, 3, 5, 10, and 28, we determined the expression of HLA-DR in monocytes and the apoptosis and the proliferation index in T lymphocytes, as well as the levels of tumor necrosis factor-α, interleukin-6, interleukin-1β, interleukin-10, and transforming growth factor-β in both plasma and cell culture supernatants of peripheral blood mononuclear cells. The mean percentage of HLA-DR+ was 60.7 at enrollment and increased by 0.9% (95% CI, 0.7–1.2%) per day. The mean percentage of CD4 T cells and CD8 T cells AV+/7-AAD– at enrollment was 37.2% and 20.4%, respectively, but it diminished at a rate of –0.5% (95% CI, –0.7% to –0.3%) and –0.3% (95% CI, –0.4% to –0.2%) per day, respectively. Plasma levels of interleukin-6 and interleukin-10 were 290 and 166 pg/mL and decreased at a rate of –7.8 pg/mL (95% CI, –9.5 to –6.1 pg/mL) and –4 pg/mL (95% CI, –5.1 to –2.8 pg/mL) per day, respectively. After controlling for confounders, only sustained plasma levels of interleukin-6 increase the risk of death (hazard ratio 1.003; 95% CI, 1.001–1.006).

Conclusions:

We found no evidence to support a two-phase model of sepsis pathophysiology. However, immunological variables did behave in a mixed and time-dependent manner. Further studies should evaluate changes over time of interleukin-6 plasma levels as a prognostic biomarker for critically ill patients.

Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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