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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

doi: 10.1097/CCM.0000000000000100
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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.

1Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

2Grupo Académico de Epidemiologia Clínica, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

3Departamento de Ciencias Básicas, Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, Colombia.

4Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

5Departamento de Medicina Interna, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

6Unidad de Investigaciones, Hospital Pablo Tobón Uribe, Medellín, Colombia.

* See also p. 972.

This work was performed at Universidad de Antioquia and Hospital Universitario San Vicente Fundación, Medellín, Colombia.

Mr. Gomez, Ms. Gonzalez, Dr. Londoño, Dr. Hoyos, Dr. Niño, and Ms. León’s institutions received grant support from Colciencias (111551928175). Ms. Velilla, Ms. Rugeles, and Dr. Jaimes are employed by the Universidad de Antioquia and their institutions received grant support from Colciencias (111551928175).

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