Toll-like receptor responses are suppressed in trauma ICU patients

J Surg Res. 2016 Nov;206(1):139-145. doi: 10.1016/j.jss.2016.06.056. Epub 2016 Jun 25.

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.

Keywords: Cytokines; DAMPS; Inflammation; PAMPs; Whole blood.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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