title: Toll-like receptor responses are suppressed in trauma ICU patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas.
authors.forename: Travis L
authors.initials: TL
authors.lastname: Holloway
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas.
authors.forename: Susannah E
authors.initials: SE
authors.lastname: Nicholson
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rani
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas; Blood Research, US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas; Blood Research, US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas. Electronic address: schwacha@uthscsa.edu.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012475:Salmonella; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology*; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology*; D055815:Young Adult; D015054:Zymosan / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015054:Zymosan
keywords: Cytokines; DAMPS; Inflammation; PAMPs; Whole blood