Toll-like receptor responses are suppressed in trauma ICU patients.

Abstract

BACKGROUND:

Inflammation and activation of the innate immune system are often associated with traumatic injury and may involve alterations in toll-like receptor (TLR)-mediated responses.

METHODS:

A prospective observational study was designed and conducted. Twenty-one severely injured (ISS = 16-41) trauma intensive care unit (ICU) patients and six healthy volunteers that served as controls were enrolled. Anticoagulated whole blood was collected at 2-12 d after ICU admission and incubated in the presence of media alone (baseline), zymosan (TLR2 agonist) or lipopolysaccharide (LPS; TLR4 agonist) for 3 h. Supernatant levels of inflammatory cytokines (IL-1β, IL-6, IL-10, and TNFα) were determined.

RESULTS:

TLR2-mediated and TLR4-mediated activation of whole blood cell cultures from both healthy volunteers and subjects-induced elevated cytokine levels over that observed in unstimulated cultures. Baseline values of IL-6 were significantly elevated in subject cultures as compared to healthy volunteers. Healthy volunteer cultures had 2-3-fold greater levels of IL-6 and TNFα than subject cultures when stimulated with zymosan (TLR2 agonist) or LPS (TLR4 agonist). IL-1β and IL-10 levels did not differ significantly between healthy volunteers and subjects.

CONCLUSIONS:

The ability of circulating leukocytes from trauma ICU patients to be activated by TLR agonists is markedly suppressed and may play a role in the development of subsequent infectious complications.

• Authors: Travis L Holloway, Susannah E Nicholson, Meenakshi Rani, Andrew P Cap, Martin G Schwacha
• Journal: The Journal of surgical research (J Surg Res) Vol. 206 Issue 1 Pg. 139-145 (11 2016) ISSN: 1095-8673 [Electronic] United States
• PMID: 27916353 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cytokines
• Lipopolysaccharides
• TLR2 protein, human
• TLR4 protein, human
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Zymosan

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Case-Control Studies
• Cytokines (blood)
• Female
• Humans
• Intensive Care Units
• Leukocytes (drug effects, immunology, metabolism)
• Lipopolysaccharides (pharmacology)
• Male
• Middle Aged
• Prospective Studies
• Salmonella
• Toll-Like Receptor 2 (agonists, immunology)
• Toll-Like Receptor 4 (agonists, immunology)
• Wounds and Injuries (blood, immunology)
• Young Adult
• Zymosan (pharmacology)