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The Involvement of Danger-Associated Molecular Patterns in the Development of Immunoparalysis in Cardiac Arrest Patients.
- Source :
-
Critical Care Medicine . Nov2015, Vol. 43 Issue 11, p2332-2338. 7p. - Publication Year :
- 2015
-
Abstract
- <bold>Objectives: </bold>After cardiac arrest, patients are highly vulnerable toward infections, possibly due to a suppressed state of the immune system called "immunoparalysis." We investigated if immunoparalysis develops following cardiac arrest and whether the release of danger-associated molecular patterns could be involved. <bold>Design: </bold>Observational study. <bold>Setting: </bold>ICU of a university medical center. <bold>Patients: </bold>Fourteen post-cardiac arrest patients treated with mild therapeutic hypothermia for 24 hours and 11 control subjects. <bold>Measurements and Main Results: </bold>Plasma cytokines showed highest levels within 24 hours after cardiac arrest and decreased during the next 2 days. By contrast, ex vivo production of cytokines interleukin-6, tumor necrosis factor-α, and interleukin-10 by lipopolysaccharide-stimulated leukocytes was severely impaired compared with control subjects, with most profound effects observed at day 0, and only partially recovering afterward. Compared with incubation at 37°C, incubation at 32°C resulted in higher interleukin-6 and lower interleukin-10 production by lipopolysaccharide-stimulated leukocytes of control subjects, but not of patients. Plasma nuclear DNA, used as a marker for general danger-associated molecular pattern release, and the specific danger-associated molecular patterns (EN-RAGE and heat shock protein 70) were substantially higher in patients at days 0 and 1 compared with control subjects. Furthermore, plasma heat shock protein 70 levels were negatively correlated with ex vivo production of inflammatory mediators interleukin-6, tumor necrosis factor-α, and interleukin-10. Extracellular newly identified receptor for advanced glycation end products-binding protein levels only showed a significant negative correlation with ex vivo production of interleukin-6 and tumor necrosis factor-α and a borderline significant inverse correlation with interleukin-10. No significant correlations were observed between plasma nuclear DNA levels and ex vivo cytokine production. <bold>Interventions: </bold>None. <bold>Conclusions: </bold>Release of danger-associated molecular patterns during the first days after cardiac arrest is associated with the development of immunoparalysis. This could explain the increased susceptibility toward infections in cardiac arrest patients. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ACADEMIC medical centers
*AGE distribution
*ARTIFICIAL respiration
*CARDIOPULMONARY resuscitation
*CATASTROPHIC illness
*CRITICAL care medicine
*CYTOKINES
*INDUCED hypothermia
*IMMUNOLOGICAL tolerance
*INTENSIVE care units
*INTERLEUKINS
*LONGITUDINAL method
*MEMBRANE proteins
*NONPARAMETRIC statistics
*SCIENTIFIC observation
*POLYMERASE chain reaction
*REFERENCE values
*SEX distribution
*SURVIVAL
*T-test (Statistics)
*DATA analysis software
*HOSPITAL mortality
*MANN Whitney U Test
*ONE-way analysis of variance
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 00903493
- Volume :
- 43
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Critical Care Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 110348860
- Full Text :
- https://doi.org/10.1097/CCM.0000000000001204